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NKX2-1 (NK2 homeobox 1)

Written2010-04Theresia Wilbertz, Sebastian Maier, Sven Perner
Institute of Pathology, University Hospital Tubingen, Germany

(Note : for Links provided by Atlas : click)

Identity

Alias_namesNKX2A
BCH
TITF1
benign chorea
thyroid transcription factor 1
Alias_symbol (synonym)TTF-1
TTF1
Other aliasBHC
NK-2
NKX2.1
TEBP
HGNC (Hugo) NKX2-1
LocusID (NCBI) 7080
Atlas_Id 44015
Location 14q13.3  [Link to chromosome band 14q13]
Location_base_pair Starts at 36516399 and ends at 36520225 bp from pter ( according to hg19-Feb_2009)  [Mapping NKX2-1.png]
Fusion genes
(updated 2016)
BAZ1A (14q13.1) / NKX2-1 (14q13.3)NKX2-1 (14q13.3) / SFTA3 (14q13.3)NKX2-1 (14q13.3) / SLC25A21 (14q13.3)
SFTA3 (14q13.3) / NKX2-1 (14q13.3)

DNA/RNA

 
  Figure 1. NKX2-1 gene and NKX2-1 mRNA.
Description NKX2-1 is regulated by two promoter regions: the first one is located in intron 1 (5' of exon 1, regulation of NKX2-1 in lung and thyroid cells). The second one is situated in the 5' flanking region of exon 1, it is a 330 bp TATA-less region containing multiple palindromes and G/C-rich elements. It regulates NKX2-1 in lung epithelial cells responding to transcription factors sp1 and sp3.
Transcription NKX2-1 is transcribed in two highly conserved forms: mRNA-isoform 1 contains exon 1, exon 2, and exon 3, it is translated into a 401 amino acid protein and represents the minor transcript. mRNA-isoform 2 is the predominant transcript containing exon 2 and exon 3. It is translated into a 371 aa protein.

Protein

 
  Figure 2. Upstream and downstream targets of NKX2-1.
Description The NKX2-1 protein includes three functional domains: an N-terminal transactivation domain, a DNA-binding transactivation domain and a C-terminal transactivation domain.
Expression In the lung, expression of NKX2-1 is consistent throughout all life stages from fetal to adult tissue. It is expressed in conducting airways type II alveolar epithelial cells and Clara cells and uniformly in the terminal respiratory unit.
NKX2-1 expression is also found in thyroid follicular cells and both normal and hyperplastic C cells where it activates calcitonin gene expression.
NKX2-1 is not expressed in adult neurons of the basal ganglia.
During embryonic and fetal development, NKX2-1 expression is found in various tissues (e.g. brain, lung, thyroid), for details see "function" → "Embryonic and fetal development".
Localisation NKX2-1 is a nuclear transcription factor.
Function In the lung, NKX2-1 regulates the expression of the lung-specific genes: surfactant protein SP-A, SP-B, SP-C and Clara cell secretory protein (CCSP).
It cooperates with C/EBPalpha in transactivating CCSP.
In the transcription of SP-C, NKX2-1 interacts with nuclear factor I to differentially regulate the transcription. The longer NKX2-1 isoform reduces transactivation of SP-C, probably due to some kind of interference.
NKX2-1 is a key activator of SP-B gene expression having at least two binding sites at the SP-B promoter and enhancer. The transactivation capacity of NKX2-1 regarding the expression of SP-B is controlled by the sphingolipid ceramide which is produced in inflammation and reduces NKX2-1 binding capacity to the SP-B promoter. SP-B transcription is also inhibited by TGFbeta1-mediated interaction of smad3 with NKX2-1. Moreover, NKX2-1 interacts with retinoic acid receptor (RAR), nuclear receptor coactivators (p160, CBP/p300) and signal transducers and activators of transcription 3 (STAT3) in regulation of SP-B expression.
Furthermore, NKX2-1 regulates the expression of the secretoglobulin 3A2 gene (SCGB3A2) in mouse airways in cooperation with CAATT/enhancer binding proteins alpha and delta as well as the expression of ABCA3 which encodes for a lipid transporter critical for surfactant function at birth and formation of lamellar bodies.

NKX2-1 also plays an important role in the endocrine system: it regulates the expression of the thyroid-specific genes thyroglobulin, thyroid peroxidase, thyrotropin receptor and sodium-iodide-symporter, therefore being crucial for proper thyroid hormone synthesis.
Deletion of NKX2-1 in differentiated neurons of the hypothalamus in mice causes delayed puberty, reduced reproductive capacity and a shorter reproductive span in female mice, suggesting that NKX2-1 plays an important role in juvenile and adult endocrine function.
During embryonic and fetal development, NKX2-1 is active in various organs, especially lung, thyroid and brain.
As a crucial factor for lung development, NKX2-1 is expressed in the ventral foregut endoderm at a very early stage functioning as a signal which is essential for specification of a pulmonary cell fate instead of a liver cell fate. At a later stage, NKX2-1 is critical to the formation of distal pulmonary structures (whereas proximal lung differentiation is NKX2-1-independent), a function in which it is inhibited by TGF-beta.
In addition to that NKX2-1 regulates surfactant protein genes that are important for the development of alveolar stability at birth. It induces SP-A gene expression in fetal lung type II cells through increased binding of NKX2-1 (mediated by cAMP) and the NFkappa-B proteins p50 and p65. Supporting the notion of NKX2-1-dependent SP-expression, lung and associated respiratory dysfunction in neonates caused by SP-B-deficiency are partly induced by down-regulation of NKX2-1. The main therapeutical option, prenatal glucocorticoid treatment, induces the expression of NKX2-1. NKX2-1 regulates expression of uteroglobin-related protein-1 and claudin-18 during lung development.
During thyroid gland organogenesis NKX2-1 is expressed in the ultimobranchial body (UBB) and in the thyroid diverticulum. It is important for the survival of UBB-cells and eventually their dissemination into the thyroid diverticulum and for the formation of the UBB-derived vesicular structure. Pendrin and thyroglobulin are downstream targets of NKX2-1 during thyroid differentiation. The transactivational activity of NKX2-1 during thyroid development can be inhibited by NKX2-5.
In the course of brain development, NKX2-1 expression is found in both telencephalic and diencephalic domains. It cooperates with Gsh2 to pattern the ventral telencephalon. Lack of functional NKX2-1 protein in neurons impairs developmental differentiation and organization of basal ganglia and basal forebrain. NKX2-1 upregulates the transcription of nestin, an intermediate filament protein expressed in multipotent neuroepithelial cells, by direct binding to a HRE-CRE-like site (NestBS) within a CNS-specific enhancer, which indicates that nestin might be at least one of the effectors of NKX2-1 during forebrain development.
NKX2-1 expression occurs in neurons of the arcuate nucleus of the hypothalamus and in glia cells (tanycytes) in neonatal and adult mice, as well as in fetal and adult pituicytes suggesting that NKX2-1 is essential for proper development of the hypothalamus. Lack of NKX2-1 causes aberrant trajectory of the dopaminergic pathway in the developing hypothalamus (mouse-model), development of GABAergic and cholinergic neurons is also impaired in NKX2-1 defective mice. Furthermore, NKX2-1 regulates the specification of oligodendrocytes and controls the postmitotic migration of interneurons originating in the medial ganglionic eminence to either the cortex (downregulation of NKX2-1) or the striatum (maintenance of NKX2-1 expression and thus direct transcriptional activation of neuropilin-2, a guidance receptor in postmitotic cells). By directly activating Lhx6 during embryonic development NKX2-1 plays an essential role for the specification of cortical interneurons which express parvalbumin or somatostatin.

In accordance with the findings concerning the role of NKX2-1 in the development of the above-mentioned organs, NKX2-1-defective mice die at birth due to a characteristic set of malformations and functional impairments: hypoplastic lungs and insufficient surfactant production, defective hypothalamus, absence of thyroid and pituitary gland, delayed development of dopaminergic, GABAergic and cholinergic neurons.

Mutations

Note
Brain-lung-thyroid syndrome
congenital hypothyreoidism, infant respiratory distress syndrome, benign hereditary chorea
SNPbp 523G → Tpremature stop codon at postition 175
SNPbp 609C → Apremature stop codon at position 145
SNPbp 1320C → Apremature stop codon at position 75
SNPbp 2626G → Tmissense mutation: valine → phenylalanine at position 14 of DNA-binding-domain
SNPsplice acceptor site of intron 2A → Taltered mRNA structure => incorrect removal of introns
Deletion14q11.2-q13.3
Insertionbp 2595insertion of GG frameshift mutation: causes truncated protein lacking the entire third helix of the homeodomain
Cancer predisposition
can contribute to predisposition for multinodular goiter and papillary thyroid carcinoma.
SNPbp 1016C → Tmissense mutation: A339V
Table 1. Mutations in NKX2-1 gene.
Germinal Mutations in NKX2-1 (for details see table 1) can cause benign hereditary chorea (BHC, a dyskinesia, i.e. a neurological disorder characterized by abnormal involuntary movements) and brain-lung-thyroid syndrome (in addition to BHC, patients suffer from congenital hypothyroidism and infant respiratory distress syndrome).

A heterozygous substitution at position 1016 in the coding sequence (C → T) leads to a mutant NKX2-1 protein (A339V) and can contribute to a predisposition for multinodular goiter and papillary thyroid carcinoma. For other heterozygous NKX2-1 mutations in humans, phenotypes vary widely.
Thyroid dysfunction ranges from mild hypothyrotrophinaemia to severe congenital hypothyroidism due to thyroid hypoplasia or even agenesis. Implication of the lung ranges from a slight increase in pulmonary infections to severe neonatal respiratory distress syndrome.

Homozygous NKX2-1 mutations in humans are probably not viable.

Implicated in

Note
  
Entity Various cancers
Note NKX2-1 expression has been found in a variety of tumor entities, especially lung and thyroid tumors (for details see table 2).
Disease
Consistently expressed
Occasionally expressed
Not expressed
Thyroid
- Papillary carcinoma
- Follicular carcinoma
- Medullary carcinoma
- Hurthle cell carcinoma
- Follicular adenoma
- Hyperplastic follicular cells
- Undifferentiated thyroid carcinomas
Lung
- Adenocarcinoma
- Small cell lung cancer (SCLC)
- Pleural effusions of SCLC
- Pulmonary sclerosing hemangioma
- Bronchioloalveolar carcinoma (except for mucinous parts)
- Non-neuroendocrine large-cell carcinoma
- Signet-ring cell carcinomas of lung origin
- Pulmonary carcinoids (50%) - Squamous cell lung cancer
- Pleural mesothelioma
- Bronchioloalveolar carcinomas (just mucinous parts)
- Basaloid carcinoma of the lung
Gastrointestinal system
- Small cell cancer of the esophagus - Colorectal carcinoma
Genitourinary system
- Small cell carcinoma of the urine bladder
- Nephroblastoma
- Endometrial carcinoma
- Endocervical carcinoma
Thymus
- Thymic carcinoma
- Thymoma
Skin
- Merkel cell carcinoma
Neuroectodermal
- Ependymoma
- Glioblastoma
- Astrocytoma
- Oligodendroglioma
- Medulloblastoma
- Paraganglioma
- Ganglioglioma
Neuroendocrine
(carcinoid tumorlets, neuroendocrine cell hyperplasia, typical carcinoids, atypical carcinoids, large cell neuroendocrine carcinomas)
- Thyroid origin
- Pulmonary origin
- Thymic origin
- Gastrointestinal origin
- Pancreatic origin
- Ovarian origin
- Parathyroid adenoma
- Pituitary adenoma
- Pheochromocytoma
Body cavity fluids
- Lung origin (adenocarcinoma) - Genitourinary origin
- Gastrointestinal origin
- Breast origin
- Ovarian origin

Table 2. Expression of NKX2-1 in different tumor entities.
  
  
Entity Lung neoplasms
Disease NKX2-1 is strongly expressed in 75-90% of primary lung adenocarcinomas, whereas only 1/4 of bronchioloalveolar carcinomas show NKX2-1 positivity. Among non-small cell lung cancers, NKX2-1 is not expressed in squamous cell lung cancer.
Small cell lung cancer, as well as pulmonary carcinoids and non-neuroendocrine large-cell carcinomas partly exhibit NKX2-1 protein expression.
Prognosis Overall, NKX2-1 expression is a predictor for better survival in adenocarcinomas of the lung (just one smaller study suggested that NKX2-1 expression is associated with poor prognosis). Controversially, NKX2-1 pathway activation in lung cancers is associated with poor survival and cisplatin resistance if PAX9 or Nkx2-8 pathways are activated at the same time.
Oncogenesis NKX2-1 is highly amplified in 5-15% of primary lung adenocarcinomas. In cells harbouring NKX2-1 amplification, this recurrent gene amplification seems to be a mechanism of high-level NKX2-1 expression.
For a subset of lung adenocarcinomas (especially those which are derived from the terminal respiratory unit) sustained expression of NKX2-1 has been shown to be crucial for the survival of tumor cells. In these tumors RNAi inhibition of NKX2-1 induces proliferation inhibition, growth inhibition and apoptosis (lineage-specific dependency model).
Interestingly, NKX2-1 is also an activator of HOP (Hsp70/Hsp90 Organizing Protein), a potential tumor suppressor gene in lung cancer, and it inhibits EMT (epithelial to mesenchymal transition). NKX2-1 restores epithelial phenotypes in lung adenocarcinomas, acting as an adversary of the EMT-stimulating TGF-beta and a suppressor of tumor progression and invasiveness. TGF-beta inhibits the expression of NKX2-1 and thus lung morphogenesis.
Moreover, NKX2-1 is expressed in most metastatic lung adenocarcinomas.
  
  
Entity Thyroid neoplasms
Disease Well-differentiated thyroid follicular cell tumors, such as follicular adenomas, follicular carcinomas and papillary carcinomas exhibit strong nuclear positivity for NKX2-1 staining. In contrast, undifferentiated thyroid carcinomas show low or no immunoreaction.
Concerning parafollicular cells, NKX2-1 expression can be found in normal and hyperplastic c-cells, as well as in medullary thyroid carcinomas. However, the signal intensity is much weaker and less homogenous than observed in tumors originating from follicular thyroid cells.
Non-malignant branchiogenic cysts can easily be confounded with papillary thyroid carcinomas. Since positive immunostaining for NKX2-1 has been found in a subset of these non-malignant cervical cysts, NKX2-1 cannot serve to distinguish between both entities.
Oncogenesis NKX2-1 is expressed in most differentiated thyroid neoplasms, but not in undifferentiated tumors of thyroid origin. On DNA-level, normal thyroids and papillary carcinomas do not exhibit DNA methylation in the CpG of NKX2-1 promoter, whereas undifferenciated thyroid carcinomas show DNA methylation in this region in about 60%. Most metastases of thyroid origin are positive for NKX2-1 expression.
A heterozygous germline mutation, which leads to a mutant NKX2-1 protein has been shown to be associated with increased cell proliferation. Consequently, it might contribute to a predisposition for multinodular goiter and papillary thyroid carcinoma (for details see section mutations).
  
  
Entity Neoplasms of the gastrointestinal tract
Disease Small cell esophageal cancers exhibit NKX2-1 expression in the majority of cases. In contrast, carcinoids originating from the gastrointestinal tract, such as ileal, appendical, duodenal, ampullary, rectal, pancreatic and gastric carcinoids are negative for NKX2-1 immunohistochemical staining.
  
  
Entity Neoplasms of the genitourinary tract
Disease NKX2-1 seems to be implicated in neoplasms arising from the urinary system. Small cell carcinomas of the urinary bladder are positive for NKX2-1 staining in 25-40% of cases. Likewise, large cell neuroendocrine bladder carcinomas exhibit NKX2-1 expression. In one study, 1/6 of a set of nephroblastomas showed nuclear positivity for NKX2-1, whereas metanephric adenomas and cystic nephromas were NKX2-1 negative.
NKX2-1 expression can be found in benign tubal and endometrial epithelia, as well as in benign tumors originating from these tissues. In addition, malignant tumors of the female genital tract, such as endocervical adenocarcinomas, small cell carcinomas of the uterine cervix, endometrioid adenocarcinomas, serous carcinomas, clear cell carcinomas, and uterine malignant mixed Mullerian tumors show positivity for NKX2-1. Staining morphology in these tumors differs from rare positive cells to a diffusely positive staining pattern.
Prognosis No correlation could be detected between positive NKX2-1 immunostaining in small cell carcinomas of the urinary bladder and clinicopathologic features (including outcome, age, sex, smoking history, stage and metastatic status).
  
  
Entity Neuroendocrine neoplasms
Disease Among well-differentiated neuroendocrine tumors, only those tumors originating from the lung or thyroid are positive for NKX2-1 expression. Neither gastrointestinal typical or atypical carcinoids, nor neuroendocrine tumors from other sites (e.g. Merkel cell carcinomas, thymic carcinoids, ovarian large cell neuroendocrine carcinomas) show NKX2-1 expression.
Concerning small cell carcinomas, NKX2-1 expression is not specific for small cell lung cancer, as NKX2-1 expression can also be found in small cell carcinomas originating from the esophagus, prostate, bladder or uterine cervix.
  
  
Entity Neoplasms of neuroectodermal origin
Disease NKX2-1 occasionally has been detected in glioblastoma multiforme and in ependymomas of the third ventricle. Other primary brain tumors, such as astrocytomas, oligodendrogliomas, medulloblastomas and gangliomas from various sites do not exhibit NKX2-1 expression.
Sellar tumors, including pituicytomas, atypical pituicytomas, granular cell tumors and spindle cell oncocytomas can show positive immunostaining for NKX2-1.
  

To be noted

NKX2-1 has been well studied in neoplasms of the lung and thyroid, but lacks a sufficient level of evidence in other tumor entities.

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PMID 16960125
 
Epigenetic silencing of TTF-1/NKX2-1 through DNA hypermethylation and histone H3 modulation in thyroid carcinomas.
Kondo T, Nakazawa T, Ma D, Niu D, Mochizuki K, Kawasaki T, Nakamura N, Yamane T, Kobayashi M, Katoh R.
Lab Invest. 2009 Jul;89(7):791-9. Epub 2009 Jun 8.
PMID 19506552
 
Thyroid transcription factor 1 expression in cystic lesions of the neck: an immunohistochemical investigation of thyroglossal duct cysts, branchial cleft cysts and metastatic papillary thyroid cancer.
Kreft A, Hansen T, Kirkpatrick CJ.
Virchows Arch. 2005 Jul;447(1):9-11. Epub 2005 Jun 10.
PMID 15947946
 
Choreoathetosis, hypothyroidism, and pulmonary alterations due to human NKX2-1 haploinsufficiency.
Krude H, Schutz B, Biebermann H, von Moers A, Schnabel D, Neitzel H, Tonnies H, Weise D, Lafferty A, Schwarz S, DeFelice M, von Deimling A, van Landeghem F, DiLauro R, Gruters A.
J Clin Invest. 2002 Feb;109(4):475-80.
PMID 11854319
 
Thyroid transcription factor-1 expression in ovarian epithelial neoplasms.
Kubba LA, McCluggage WG, Liu J, Malpica A, Euscher ED, Silva EG, Deavers MT.
Mod Pathol. 2008 Apr;21(4):485-90. Epub 2008 Feb 1.
PMID 18246044
 
Growth factors in lung development.
Kumar VH, Lakshminrusimha S, El Abiad MT, Chess PR, Ryan RM.
Adv Clin Chem. 2005;40:261-316. (REVIEW)
PMID 16355925
 
Thyroid-specific enhancer-binding protein/NKX2.1 is required for the maintenance of ordered architecture and function of the differentiated thyroid.
Kusakabe T, Kawaguchi A, Hoshi N, Kawaguchi R, Hoshi S, Kimura S.
Mol Endocrinol. 2006 Aug;20(8):1796-809. Epub 2006 Apr 6.
PMID 16601074
 
Genomic profiling identifies TITF1 as a lineage-specific oncogene amplified in lung cancer.
Kwei KA, Kim YH, Girard L, Kao J, Pacyna-Gengelbach M, Salari K, Lee J, Choi YL, Sato M, Wang P, Hernandez-Boussard T, Gazdar AF, Petersen I, Minna JD, Pollack JR.
Oncogene. 2008 Jun 5;27(25):3635-40. Epub 2008 Jan 21.
PMID 18212743
 
Expression of thyroid transcription factor-1, cytokeratin 7, and cytokeratin 20 in bronchioloalveolar carcinomas: an immunohistochemical evaluation of 67 cases.
Lau SK, Desrochers MJ, Luthringer DJ.
Mod Pathol. 2002 May;15(5):538-42.
PMID 12011259
 
Thyroid transcription factor 1 expression in sellar tumors: a histogenetic marker?
Lee EB, Tihan T, Scheithauer BW, Zhang PJ, Gonatas NK.
J Neuropathol Exp Neurol. 2009 May;68(5):482-8.
PMID 19525896
 
Two functionally distinct forms of NKX2.1 protein are expressed in the pulmonary epithelium.
Li C, Cai J, Pan Q, Minoo P.
Biochem Biophys Res Commun. 2000 Apr 13;270(2):462-8.
PMID 10753648
 
A novel DNA element mediates transcription of Nkx2.1 by Sp1 and Sp3 in pulmonary epithelial cells.
Li C, Ling X, Yuan B, Minoo P.
Biochim Biophys Acta. 2000 Feb 29;1490(3):213-24.
PMID 10684967
 
Thyroid transcription factor-1 in the histogenesis of plumonary sclerosing hemangioma.
Lin D, Zou S, Lu N, Liu X, Wen P, Li L.
Zhonghua Zhong Liu Za Zhi. 2002 Jul;24(4):384-7.
PMID 12408771
 
Thyroglobulin and human thyroid cancer.
Lin JD.
Clin Chim Acta. 2008 Feb;388(1-2):15-21. Epub 2007 Nov 12. (REVIEW)
PMID 18060877
 
Diagnostic value of CDX-2 and TTF-1 expressions in separating metastatic neuroendocrine neoplasms of unknown origin.
Lin X, Saad RS, Luckasevic TM, Silverman JF, Liu Y.
Appl Immunohistochem Mol Morphol. 2007 Dec;15(4):407-14.
PMID 18091383
 
Down-regulation of thyroid transcription factor-1 gene expression in fetal lung hypoplasia is restored by glucocorticoids.
Losada A, Tovar JA, Xia HM, Diez-Pardo JA, Santisteban P.
Endocrinology. 2000 Jun;141(6):2166-73.
PMID 10830305
 
Immunohistochemical expression of TTF-1 in various cytological subtypes of primary lung adenocarcinoma, with special reference to intratumoral heterogeneity.
Maeshima AM, Omatsu M, Tsuta K, Asamura H, Matsuno Y.
Pathol Int. 2008 Jan;58(1):31-7.
PMID 18067638
 
Molecular interactions coordinating the development of the forebrain and face.
Marcucio RS, Cordero DR, Hu D, Helms JA.
Dev Biol. 2005 Aug 1;284(1):48-61.
PMID 15979605
 
Deletion of the Ttf1 gene in differentiated neurons disrupts female reproduction without impairing basal ganglia function.
Mastronardi C, Smiley GG, Raber J, Kusakabe T, Kawaguchi A, Matagne V, Dietzel A, Heger S, Mungenast AE, Cabrera R, Kimura S, Ojeda SR.
J Neurosci. 2006 Dec 20;26(51):13167-79.
PMID 17182767
 
Primary signet-ring cell carcinoma of lung: immunohistochemical study and comparison with non-pulmonary signet-ring cell carcinomas.
Merchant SH, Amin MB, Tamboli P, Ro J, Ordonez NG, Ayala AG, Czerniak BA, Ro JY.
Am J Surg Pathol. 2001 Dec;25(12):1515-9.
PMID 11717541
 
The synergistic activity of thyroid transcription factor 1 and Pax 8 relies on the promoter/enhancer interplay.
Miccadei S, De Leo R, Zammarchi E, Natali PG, Civitareale D.
Mol Endocrinol. 2002 Apr;16(4):837-46.
PMID 11923479
 
The role of TTF-1 in differentiating primary and metastatic lung adenocarcinomas.
Moldvay J, Jackel M, Bogos K, Soltesz I, Agocs L, Kovacs G, Schaff Z.
Pathol Oncol Res. 2004;10(2):85-8. Epub 2004 Jun 9.
PMID 15188024
 
Pituitary hypoplasia and respiratory distress syndrome in Prop1 knockout mice.
Nasonkin IO, Ward RD, Raetzman LT, Seasholtz AF, Saunders TL, Gillespie PJ, Camper SA.
Hum Mol Genet. 2004 Nov 15;13(22):2727-35. Epub 2004 Sep 30.
PMID 15459176
 
A germline mutation (A339V) in thyroid transcription factor-1 (TITF-1/NKX2.1) in patients with multinodular goiter and papillary thyroid carcinoma.
Ngan ES, Lang BH, Liu T, Shum CK, So MT, Lau DK, Leon TY, Cherny SS, Tsai SY, Lo CY, Khoo US, Tam PK, Garcia-Barcelo MM.
J Natl Cancer Inst. 2009 Feb 4;101(3):162-75. Epub 2009 Jan 27.
PMID 19176457
 
UGRP1, a uteroglobin/Clara cell secretory protein-related protein, is a novel lung-enriched downstream target gene for the T/EBP/NKX2.1 homeodomain transcription factor.
Niimi T, Keck-Waggoner CL, Popescu NC, Zhou Y, Levitt RC, Kimura S.
Mol Endocrinol. 2001 Nov;15(11):2021-36.
PMID 11682631
 
claudin-18, a novel downstream target gene for the T/EBP/NKX2.1 homeodomain transcription factor, encodes lung- and stomach-specific isoforms through alternative splicing.
Niimi T, Nagashima K, Ward JM, Minoo P, Zimonjic DB, Popescu NC, Kimura S.
Mol Cell Biol. 2001 Nov;21(21):7380-90.
PMID 11585919
 
Postmitotic Nkx2-1 controls the migration of telencephalic interneurons by direct repression of guidance receptors.
Nobrega-Pereira S, Kessaris N, Du T, Kimura S, Anderson SA, Marin O.
Neuron. 2008 Sep 11;59(5):733-45.
PMID 18786357
 
Thyroid transcription factor-1 distinguishes metastatic pulmonary from well-differentiated neuroendocrine tumors of other sites.
Oliveira AM, Tazelaar HD, Myers JL, Erickson LA, Lloyd RV.
Am J Surg Pathol. 2001 Jun;25(6):815-9.
PMID 11395561
 
Expression of calretinin and other mesothelioma-related markers in thymic carcinoma and thymoma.
Pan CC, Chen PC, Chou TY, Chiang H.
Hum Pathol. 2003 Nov;34(11):1155-62.
PMID 14652817
 
TTF-1/NKX2.1 up-regulates the in vivo transcription of nestin.
Pelizzoli R, Tacchetti C, Luzzi P, Strangio A, Bellese G, Zappia E, Guazzi S.
Int J Dev Biol. 2008;52(1):55-62.
PMID 18033672
 
TTF1 expression in non-small cell lung carcinoma: association with TTF1 gene amplification and improved survival.
Perner S, Wagner PL, Soltermann A, LaFargue C, Tischler V, Weir BA, Weder W, Meyerson M, Giordano TJ, Moch H, Rubin MA.
J Pathol. 2009 Jan;217(1):65-72.
PMID 18932182
 
Combined analysis of MIB-1 and thyroid transcription factor-1 predicts survival in non-small cell lung carcinomas.
Puglisi F, Aprile G, Bruckbauer M, Barbone F, Damante G, Guerra S, Beltrami CA, Di Loreto C.
Cancer Lett. 2001 Jan 10;162(1):97-103.
PMID 11121867
 
Thyroid-specific transcription factors control Hex promoter activity.
Puppin C, D'Elia AV, Pellizzari L, Russo D, Arturi F, Presta I, Filetti S, Bogue CW, Denson LA, Damante G.
Nucleic Acids Res. 2003 Apr 1;31(7):1845-52.
PMID 12655000
 
Prognostic significance of thyroid transcription factor-1 expression in both early-stage conventional adenocarcinoma and bronchioloalveolar carcinoma of the lung.
Saad RS, Liu YL, Han H, Landreneau RJ, Silverman JF.
Hum Pathol. 2004 Jan;35(1):3-7.
PMID 14745718
 
Thyroid transcription factor-1 inhibits transforming growth factor-beta-mediated epithelial-to-mesenchymal transition in lung adenocarcinoma cells.
Saito RA, Watabe T, Horiguchi K, Kohyama T, Saitoh M, Nagase T, Miyazono K.
Cancer Res. 2009 Apr 1;69(7):2783-91. Epub 2009 Mar 17.
PMID 19293183
 
Usefulness of CDX2 and TTF-1 in differentiating gastrointestinal from pulmonary carcinoids.
Saqi A, Alexis D, Remotti F, Bhagat G.
Am J Clin Pathol. 2005 Mar;123(3):394-404.
PMID 15716236
 
Different thresholds of fibroblast growth factors pattern the ventral foregut into liver and lung.
Serls AE, Doherty S, Parvatiyar P, Wells JM, Deutsch GH.
Development. 2005 Jan;132(1):35-47. Epub 2004 Dec 2.
PMID 15576401
 
Thyroid transcription factor-1 expression in endometrial and endocervical adenocarcinomas.
Siami K, McCluggage WG, Ordonez NG, Euscher ED, Malpica A, Sneige N, Silva EG, Deavers MT.
Am J Surg Pathol. 2007 Nov;31(11):1759-63.
PMID 18059234
 
Ceramide decreases surfactant protein B gene expression via downregulation of TTF-1 DNA binding activity.
Sparkman L, Chandru H, Boggaram V.
Am J Physiol Lung Cell Mol Physiol. 2006 Feb;290(2):L351-8. Epub 2005 Sep 23.
PMID 16183668
 
Interleukin-10 induces uteroglobin-related protein (UGRP) 1 gene expression in lung epithelial cells through homeodomain transcription factor T/EBP/NKX2.1.
Srisodsai A, Kurotani R, Chiba Y, Sheikh F, Young HA, Donnelly RP, Kimura S.
J Biol Chem. 2004 Dec 24;279(52):54358-68. Epub 2004 Oct 13.
PMID 15485815
 
Identification of carcinoma origin by thyroid transcription factor-1 immunostaining of fine needle aspirates of metastases.
Strojan Flezar M, Srebotnik Kirbis I.
Cytopathology. 2009 Jun;20(3):176-82. Epub 2008 Mar 28.
PMID 18373697
 
Thyroid transcription factor 1 and cytokeratins 1, 5, 10, 14 (34betaE12) expression in basaloid and large-cell neuroendocrine carcinomas of the lung.
Sturm N, Lantuejoul S, Laverriere MH, Papotti M, Brichon PY, Brambilla C, Brambilla E.
Hum Pathol. 2001 Sep;32(9):918-25.
PMID 11567220
 
Functional analysis of Nkx2.1 and Pax9 for calcitonin gene transcription.
Suzuki M, Katagiri N, Ueda M, Tanaka S.
Gen Comp Endocrinol. 2007 Jun-Jul;152(2-3):259-66. Epub 2007 Feb 28.
PMID 17412341
 
Immunocytochemical profile of malignant pleural effusions of small-cell lung cancer.
Tamiolakis D, Papadopoulos N, Cheva A, Lambropoulou M, Kotini A, Mikroulis D, Didilis V, Bitzikas N, Bougioukas G.
Minerva Med. 2002 Dec;93(6):479-83.
PMID 12515971
 
Thyroid transcription factor-1 expression prevalence and its clinical implications in non-small cell lung cancer: a high-throughput tissue microarray and immunohistochemistry study.
Tan D, Li Q, Deeb G, Ramnath N, Slocum HK, Brooks J, Cheney R, Wiseman S, Anderson T, Loewen G.
Hum Pathol. 2003 Jun;34(6):597-604.
PMID 12827614
 
Lineage-specific dependency of lung adenocarcinomas on the lung development regulator TTF-1.
Tanaka H, Yanagisawa K, Shinjo K, Taguchi A, Maeno K, Tomida S, Shimada Y, Osada H, Kosaka T, Matsubara H, Mitsudomi T, Sekido Y, Tanimoto M, Yatabe Y, Takahashi T.
Cancer Res. 2007 Jul 1;67(13):6007-11.
PMID 17616654
 
CAATT/enhancer-binding proteins alpha and delta interact with NKX2-1 to synergistically activate mouse secretoglobin 3A2 gene expression.
Tomita T, Kido T, Kurotani R, Iemura S, Sterneck E, Natsume T, Vinson C, Kimura S.
J Biol Chem. 2008 Sep 12;283(37):25617-27. Epub 2008 Jul 16.
PMID 18632661
 
Comparison of the immunophenotypes of signet-ring cell carcinoma, solid adenocarcinoma with mucin production, and mucinous bronchioloalveolar carcinoma of the lung characterized by the presence of cytoplasmic mucin.
Tsuta K, Ishii G, Nitadori J, Murata Y, Kodama T, Nagai K, Ochiai A.
J Pathol. 2006 May;209(1):78-87.
PMID 16463270
 
Characterizing the cancer genome in lung adenocarcinoma.
Weir BA, Woo MS, Getz G, Perner S, Ding L, Beroukhim R, Lin WM, Province MA, Kraja A, Johnson LA, Shah K, Sato M, Thomas RK, Barletta JA, Borecki IB, Broderick S, Chang AC, Chiang DY, Chirieac LR, Cho J, Fujii Y, Gazdar AF, Giordano T, Greulich H, Hanna M, Johnson BE, Kris MG, Lash A, Lin L, Lindeman N, Mardis ER, McPherson JD, Minna JD, Morgan MB, Nadel M, Orringer MB, Osborne JR, Ozenberger B, Ramos AH, Robinson J, Roth JA, Rusch V, Sasaki H, Shepherd F, Sougnez C, Spitz MR, Tsao MS, Twomey D, Verhaak RG, Weinstock GM, Wheeler DA, Winckler W, Yoshizawa A, Yu S, Zakowski MF, Zhang Q, Beer DG, Wistuba II, Watson MA, Garraway LA, Ladanyi M, Travis WD, Pao W, Rubin MA, Gabriel SB, Gibbs RA, Varmus HE, Wilson RK, Lander ES, Meyerson M.
Nature. 2007 Dec 6;450(7171):893-8. Epub 2007 Nov 4.
PMID 17982442
 
Regulation of surfactant protein gene transcription.
Whitsett JA, Glasser SW.
Biochim Biophys Acta. 1998 Nov 19;1408(2-3):303-11. (REVIEW)
PMID 9813380
 
Cytology applications of p63 and TTF-1 immunostaining in differential diagnosis of lung cancers.
Wu M, Szporn AH, Zhang D, Wasserman P, Gan L, Miller L, Burstein DE.
Diagn Cytopathol. 2005 Oct;33(4):223-7.
PMID 16138374
 
Mechanisms of TGFbeta inhibition of LUNG endodermal morphogenesis: the role of TbetaRII, Smads, Nkx2.1 and Pten.
Xing Y, Li C, Hu L, Tiozzo C, Li M, Chai Y, Bellusci S, Anderson S, Minoo P.
Dev Biol. 2008 Aug 15;320(2):340-50. Epub 2008 May 13.
PMID 18602626
 
TTF-1 expression in pulmonary adenocarcinomas.
Yatabe Y, Mitsudomi T, Takahashi T.
Am J Surg Pathol. 2002 Jun;26(6):767-73.
PMID 12023581
 
Arcuate nucleus expression of NKX2.1 and DLX and lineages expressing these transcription factors in neuropeptide Y(+), proopiomelanocortin(+), and tyrosine hydroxylase(+) neurons in neonatal and adult mice.
Yee CL, Wang Y, Anderson S, Ekker M, Rubenstein JL.
J Comp Neurol. 2009 Nov 1;517(1):37-50.
PMID 19711380
 
Inhibition of distal lung morphogenesis in Nkx2.1(-/-) embryos.
Yuan B, Li C, Kimura S, Engelhardt RT, Smith BR, Minoo P.
Dev Dyn. 2000 Feb;217(2):180-90.
PMID 10706142
 
Primary small cell carcinoma of the esophagus: clinicopathological and immunohistochemical features of 21 cases.
Yun JP, Zhang MF, Hou JH, Tian QH, Fu J, Liang XM, Wu QL, Rong TH.
BMC Cancer. 2007 Mar 3;7:38.
PMID 17335582
 
Expression of thyroid transcription factor 1 in primary brain tumours.
Zamecnik J, Chanova M, Kodet R.
J Clin Pathol. 2004 Oct;57(10):1111-3.
PMID 15452173
 
TTF-1 expression in ovarian and uterine epithelial neoplasia and its potential significance, an immunohistochemical assessment with multiple monoclonal antibodies and different secondary detection systems.
Zhang PJ, Gao HG, Pasha TL, Litzky L, Livolsi VA.
Int J Gynecol Pathol. 2009 Jan;28(1):10-8.
PMID 19047914
 
GATA and Nkx factors synergistically regulate tissue-specific gene expression and development in vivo.
Zhang Y, Rath N, Hannenhalli S, Wang Z, Cappola T, Kimura S, Atochina-Vasserman E, Lu MM, Beers MF, Morrisey EE.
Development. 2007 Jan;134(1):189-98.
PMID 17164424
 
NKX2.1 regulates transcription of the gene for human bone morphogenetic protein-4 in lung epithelial cells.
Zhu NL, Li C, Xiao J, Minoo P.
Gene. 2004 Feb 18;327(1):25-36.
PMID 14960358
 
Comparative functional analysis provides evidence for a crucial role for the homeobox gene Nkx2.1/Titf-1 in forebrain evolution.
van den Akker WM, Brox A, Puelles L, Durston AJ, Medina L.
J Comp Neurol. 2008 Jan 10;506(2):211-23.
PMID 18022953
 

Citation

This paper should be referenced as such :
Wilbertz, Theresia ; Maier, Sebastian ; Perner, Sven
NKX2-1 (NK2 homeobox 1)
Atlas Genet Cytogenet Oncol Haematol. 2011;15(1):19-28.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/NKX2-1ID44015ch14q13.html


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 4 ]
  Thyroid: Anaplastic (undifferentiated) carcinoma
Thyroid: Medullary carcinoma
Lung: Translocations in Small Cell Carcinoma
Lung: Translocations in Squamous Cell Carcinoma


External links

Nomenclature
HGNC (Hugo)NKX2-1   11825
Cards
AtlasNKX2-1ID44015ch14q13
Entrez_Gene (NCBI)NKX2-1  7080  NK2 homeobox 1
AliasesBCH; BHC; NK-2; NKX2.1; 
NKX2A; NMTC1; T/EBP; TEBP; TITF1; TTF-1; TTF1
GeneCards (Weizmann)NKX2-1
Ensembl hg19 (Hinxton)ENSG00000136352 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000136352 [Gene_View]  chr14:36516399-36520225 [Contig_View]  NKX2-1 [Vega]
ICGC DataPortalENSG00000136352
TCGA cBioPortalNKX2-1
AceView (NCBI)NKX2-1
Genatlas (Paris)NKX2-1
WikiGenes7080
SOURCE (Princeton)NKX2-1
Genetics Home Reference (NIH)NKX2-1
Genomic and cartography
GoldenPath hg38 (UCSC)NKX2-1  -     chr14:36516399-36520225 -  14q13.3   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)NKX2-1  -     14q13.3   [Description]    (hg19-Feb_2009)
EnsemblNKX2-1 - 14q13.3 [CytoView hg19]  NKX2-1 - 14q13.3 [CytoView hg38]
Mapping of homologs : NCBINKX2-1 [Mapview hg19]  NKX2-1 [Mapview hg38]
OMIM118700   188550   600635   610978   
Gene and transcription
Genbank (Entrez)BC006221 BE796718 BM970287 BM970838 BT009773
RefSeq transcript (Entrez)NM_001079668 NM_003317
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)NKX2-1
Cluster EST : UnigeneHs.94367 [ NCBI ]
CGAP (NCI)Hs.94367
Alternative Splicing GalleryENSG00000136352
Gene ExpressionNKX2-1 [ NCBI-GEO ]   NKX2-1 [ EBI - ARRAY_EXPRESS ]   NKX2-1 [ SEEK ]   NKX2-1 [ MEM ]
Gene Expression Viewer (FireBrowse)NKX2-1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)7080
GTEX Portal (Tissue expression)NKX2-1
Protein : pattern, domain, 3D structure
UniProt/SwissProtP43699   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP43699  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP43699
Splice isoforms : SwissVarP43699
PhosPhoSitePlusP43699
Domaine pattern : Prosite (Expaxy)HOMEOBOX_1 (PS00027)    HOMEOBOX_2 (PS50071)   
Domains : Interpro (EBI)Homeobox-like    Homeobox_CS    Homeobox_dom    Homeobox_metazoa   
Domain families : Pfam (Sanger)Homeobox (PF00046)   
Domain families : Pfam (NCBI)pfam00046   
Domain families : Smart (EMBL)HOX (SM00389)  
Conserved Domain (NCBI)NKX2-1
DMDM Disease mutations7080
Blocks (Seattle)NKX2-1
SuperfamilyP43699
Human Protein AtlasENSG00000136352
Peptide AtlasP43699
HPRD02798
IPIIPI00816620   IPI00472988   IPI00974064   
Protein Interaction databases
DIP (DOE-UCLA)P43699
IntAct (EBI)P43699
FunCoupENSG00000136352
BioGRIDNKX2-1
STRING (EMBL)NKX2-1
ZODIACNKX2-1
Ontologies - Pathways
QuickGOP43699
Ontology : AmiGOnegative regulation of transcription from RNA polymerase II promoter  RNA polymerase II regulatory region sequence-specific DNA binding  RNA polymerase II regulatory region DNA binding  core promoter binding  intronic transcription regulatory region sequence-specific DNA binding  neuron migration  DNA binding  transcription factor activity, sequence-specific DNA binding  transcription factor activity, sequence-specific DNA binding  transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding  protein binding  nucleus  nucleoplasm  transcription factor complex  transcription, DNA-templated  phospholipid metabolic process  axon guidance  brain development  endoderm development  locomotory behavior  response to hormone  positive regulation of gene expression  negative regulation of epithelial to mesenchymal transition  enzyme binding  globus pallidus development  hippocampus development  cerebral cortex cell migration  forebrain dorsal/ventral pattern formation  forebrain neuron fate commitment  cerebral cortex GABAergic interneuron differentiation  pituitary gland development  lung development  negative regulation of cell migration  negative regulation of transforming growth factor beta receptor signaling pathway  thyroid gland development  thyroid gland development  forebrain development  developmental induction  Leydig cell differentiation  positive regulation of circadian rhythm  transcription regulatory region DNA binding  transcription regulatory region DNA binding  intronic transcription regulatory region DNA binding  negative regulation of transcription, DNA-templated  positive regulation of transcription, DNA-templated  positive regulation of transcription, DNA-templated  positive regulation of transcription, DNA-templated  positive regulation of transcription from RNA polymerase II promoter  rhythmic process  anatomical structure formation involved in morphogenesis  oligodendrocyte differentiation  lung saccule development  epithelial tube branching involved in lung morphogenesis  Clara cell differentiation  Type II pneumocyte differentiation  
Ontology : EGO-EBInegative regulation of transcription from RNA polymerase II promoter  RNA polymerase II regulatory region sequence-specific DNA binding  RNA polymerase II regulatory region DNA binding  core promoter binding  intronic transcription regulatory region sequence-specific DNA binding  neuron migration  DNA binding  transcription factor activity, sequence-specific DNA binding  transcription factor activity, sequence-specific DNA binding  transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding  protein binding  nucleus  nucleoplasm  transcription factor complex  transcription, DNA-templated  phospholipid metabolic process  axon guidance  brain development  endoderm development  locomotory behavior  response to hormone  positive regulation of gene expression  negative regulation of epithelial to mesenchymal transition  enzyme binding  globus pallidus development  hippocampus development  cerebral cortex cell migration  forebrain dorsal/ventral pattern formation  forebrain neuron fate commitment  cerebral cortex GABAergic interneuron differentiation  pituitary gland development  lung development  negative regulation of cell migration  negative regulation of transforming growth factor beta receptor signaling pathway  thyroid gland development  thyroid gland development  forebrain development  developmental induction  Leydig cell differentiation  positive regulation of circadian rhythm  transcription regulatory region DNA binding  transcription regulatory region DNA binding  intronic transcription regulatory region DNA binding  negative regulation of transcription, DNA-templated  positive regulation of transcription, DNA-templated  positive regulation of transcription, DNA-templated  positive regulation of transcription, DNA-templated  positive regulation of transcription from RNA polymerase II promoter  rhythmic process  anatomical structure formation involved in morphogenesis  oligodendrocyte differentiation  lung saccule development  epithelial tube branching involved in lung morphogenesis  Clara cell differentiation  Type II pneumocyte differentiation  
NDEx NetworkNKX2-1
Atlas of Cancer Signalling NetworkNKX2-1
Wikipedia pathwaysNKX2-1
Orthology - Evolution
OrthoDB7080
GeneTree (enSembl)ENSG00000136352
Phylogenetic Trees/Animal Genes : TreeFamNKX2-1
HOVERGENP43699
HOGENOMP43699
Homologs : HomoloGeneNKX2-1
Homology/Alignments : Family Browser (UCSC)NKX2-1
Gene fusions - Rearrangements
Fusion : MitelmanBAZ1A/NKX2-1 [14q13.1/14q13.3]  [t(14;14)(q13;q13)]  
Fusion : MitelmanNKX2-1/SLC25A21 [14q13.3/14q13.3]  [t(14;14)(q13;q13)]  
Fusion: TCGABAZ1A 14q13.1 NKX2-1 14q13.3 LUAD
Fusion: TCGANKX2-1 14q13.3 SLC25A21 14q13.3 LUSC
Fusion Cancer (Beijing)NKX2-1 [14q13.3]  -  SFTA3 [14q13.3]  [FUSC002382]  [FUSC002382]  [FUSC002382]  [FUSC002382]  [FUSC002382]
Fusion Cancer (Beijing)SFTA3 [14q13.3]  -  NKX2-1 [14q13.3]  [FUSC002593]  [FUSC002593]  [FUSC002593]
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerNKX2-1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)NKX2-1
dbVarNKX2-1
ClinVarNKX2-1
1000_GenomesNKX2-1 
Exome Variant ServerNKX2-1
ExAC (Exome Aggregation Consortium)NKX2-1 (select the gene name)
Genetic variants : HAPMAP7080
Genomic Variants (DGV)NKX2-1 [DGVbeta]
DECIPHERNKX2-1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisNKX2-1 
Mutations
ICGC Data PortalNKX2-1 
TCGA Data PortalNKX2-1 
Broad Tumor PortalNKX2-1
OASIS PortalNKX2-1 [ Somatic mutations - Copy number]
Cancer Gene: CensusNKX2-1 
Somatic Mutations in Cancer : COSMICNKX2-1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDNKX2-1
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
LOVD (Leiden Open Variation Database)MSeqDR-LSDB Mitochondrial Disease Locus Specific Database
BioMutasearch NKX2-1
DgiDB (Drug Gene Interaction Database)NKX2-1
DoCM (Curated mutations)NKX2-1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)NKX2-1 (select a term)
intoGenNKX2-1
NCG5 (London)NKX2-1
Cancer3DNKX2-1(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM118700    188550    600635    610978   
Orphanet905    1634    18666   
MedgenNKX2-1
Genetic Testing Registry NKX2-1
NextProtP43699 [Medical]
TSGene7080
GENETestsNKX2-1
Target ValidationNKX2-1
Huge Navigator NKX2-1 [HugePedia]
snp3D : Map Gene to Disease7080
BioCentury BCIQNKX2-1
ClinGenNKX2-1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD7080
Chemical/Pharm GKB GenePA36531
Clinical trialNKX2-1
Miscellaneous
canSAR (ICR)NKX2-1 (select the gene name)
Probes
Litterature
PubMed240 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineNKX2-1
EVEXNKX2-1
GoPubMedNKX2-1
iHOPNKX2-1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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