Atlas of Genetics and Cytogenetics in Oncology and Haematology


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Abstract

Abstract PAX2 is the second member of the nine-member PAX gene family. PAX2's role begins as a developmental gene in late primitive streak stage embryos (Dressler et al., 1990). If PAX2 becomes expressed out of its normal context, its powerful functions as a transcription factor and epigenetic regulator (reviewed in Robson et al., 2006) can be recruited to the advantage of cancer cells (Robson et al., 2006; Li and Eccles, 2012). Normally PAX2 has key roles during embryogenesis, particularly in epithelial cell differentiation from mesenchyme (Rothenpieler and Dressler, 1993), such as in kidney development, and in mammary gland ductal morphogenesis (Silberstein et al., 2002). There is a requirement for the attenuation of PAX2 expression during development, particularly for the terminal differentiation of nephrogenic precursors (Dressler et al., 1993). Following the completion of development, PAX2 is capable of being re-expressed, such as in instances of nephrotoxicity or in other kidney damage (Cohen et al., 2007). In adult tissues, PAX2 is normally expressed in the pancreas (Zaiko et al., 2004), and also in subpopulations of nodal lymphocytes (Gilmore and Dewar, 2011). When expressed out of its normal context, expression of PAX2 is frequently observed in several cancer types (Robson et al., 2006). Expression of PAX2 has been linked with cell survival (Torban et al., 2000; Muratovska et al., 2003), cell migration and invasion (Buttiglieri et al., 2004), and mesenchyme-epithelial transition (MET) and epithelial-mesenchyme transition (EMT) (Doberstein et al., 2011).

PAX2 (Paired box gene 2)

Identity

Other namesPAPRS
HGNC (Hugo) PAX2
LocusID (NCBI) 5076
Location 10q24.31
Location_base_pair Starts at 102505468 and ends at 102589698 bp from pter ( according to hg19-Feb_2009)  [Mapping]
 
  Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.

DNA/RNA

Description 12 exons, including alternative spliced exons 6 and 10 (Sanyanusin et al., 1996).
Transcription Several alternatively spliced isoforms of PAX2 have been described involving exon 6, exon 10 (Dressler et al., 1990; Ward et al., 1994), and intron 9 (Busse et al., 2009).
Pseudogene No

Protein

Note PAX2 contains a DNA binding paired domain, a truncated homeodomain, an octapeptide region and a carboxyl-terminal transactivation domain (Sanyanusin et al., 1996). Degradation/destruction of the PAX2 protein in cells is mediated by the prolyl hydroxylase domain protein 3 (PHD3) protein (Yan et al., 2011). PHD3 is also known to hydroxylate hypoxia inducible factors (HIFα) in the presence of oxygen, and leads to HIFα proteosomal degradation. In some colorectal cancer cell lines where PAX2 protein is expressed PAX2 expression was found to be elevated due to decreased PHD3 expression (Yan et al., 2011).
Description 416 amino acids; 44.7 kDa.
Expression PAX2 is expressed in the developing eye, ear, central nervous system (CNS), spinal cord, pancreas and urogenital tract (Eccles et al., 2002).
Localisation Nuclear.
Function PAX2 is a transcription factor that regulates the expression of genes involved in mediating cell proliferation and growth, resistance to apoptosis, and cell migration (Dahl et al., 1997). PAX2 null mutant mice die perinatally with absent cochlea, kidneys, ureters, oviducts, vas deferens and epididymis, and also demonstrate mid- and hindbrain deficiency and defective optic nerves (Torres et al., 1995; Torres et al., 1996). PAX2's role in normal tissues includes promoting osmotic tolerance in the adult kidney (Cai et al., 2005), determining axon number and axon trajectory in the developing optic nerve (Torres et al., 1996; Alur et al., 2008), and determining nephron number in the kidney (Dziarmaga et al., 2003; Dziarmaga et al., 2006; Clark et al., 2004). In cancer cells and in tumour endothelial cells the over-expression of PAX2 has been linked to the acquisition of a pro-invasive phenotype (Fonsato et al., 2008), and PAX2 has been suggested as a molecular target in tumour endothelial cells against which to design anti-angiogenic strategies (Bussolati et al., 2010).
Homology PAX2 shares homology through the conserved paired box domain with several other members of the nine member PAX gene family (Dahl et al., 1997; Robson et al., 2006).

Mutations

Germinal PAX2 mutations have been reported as associated with renal coloboma syndrome (see below), oligomeganephronia and isolated renal hypoplasia (Bower et al., 2012; Bower et al., 2011). These mutations are collated on the Leiden Open Variant Database platform (www.lovd.nl/PAX2). A PAX2 mutational hotspot and germline mosaiscism for PAX2 mutations have been reported (Amiel et al., 2000).

Implicated in

Entity Endometrial carcinoma
Note PAX2 is activated by oestrogen and tamoxifen in endometrial carcinomas, but not in the normal endometrium, and this activation is associated with cancer-linked hypomethylation of the PAX2 promoter (Wu et al., 2005; reviewed in Shang, 2006). In the progression from normal to endometrial precancer to cancer, the expression of both PAX2 and PTEN is progressively lost (Monte et al., 2010; Allison et al., 2012). Nevertheless, inhibition of PAX2 or silencing of PAX2 by RNAi inhibits the growth of transplanted human endometrial cancer cells in nude mice (Zhang et al., 2011).
  
Entity Breast cancer
Note PAX2 is expressed in breast cancer cell lines and tissues (Silberstein et al., 2002). A role for PAX2 in the crosstalk between estrogen receptor (ER) and ERBB2/HER-2 pathways is suggested by the observation that PAX2 is an important mediator of ER-associated repression of ERBB2 following tamoxifen treatment (Hurtado et al., 2008). PAX2 and the ER co-activator AIB-1/SRC-3 were found to compete for binding and regulation of ERBB2 transcription. Competition for binding, and dependence of the effect of tamoxifen on PAX2 is responsible for tamoxifen-responsiveness in breast cancer cells, and might suggest potential mechanisms for tamoxifen-resistance in breast cancer. PAX2 expression is negatively correlated with the recurrence of breast cancer (Liu et al., 2009), and expression of PAX2 is selectively achieved in breast cancer cells of the luminal subtype via ERα (Beauchemin et al., 2011). PAX2 has a role in maintaining a low invasive behavior in luminal breast cancer cells upon exposure to estradiol. However, in contrast to PAX2, GPR30 expression is correlated with ER expression and showed significant association with ERBB2 expression and also association with a tendency for tumour recurrence (Liu et al., 2009). An MCF-7 cell line that was selected for tamoxifen resistance resulted in several outgrowing sublines that acquired PAX2 expression, accompanied by loss of phosphorylated ERBB2, and rapamycin resistance (Leung et al., 2010).
  
Entity Ovarian carcinoma
Note PAX2 is expressed in carcinomas of the ovary (Schaner et al., 2003; Muratovska et al., 2003; Tong et al., 2007). As compared with high-grade serous ovarian carcinomas, low-grade serous carcinomas are characterized by a greater expression of PAX2 (Tung et al., 2009; Roh et al., 2010; reviewed in Gershenson, 2013). PAX2 expression was reduced in secretory cell outgrowths (SCOUTS), which are associated with serous ovarian cancer (Chen EY et al., 2010), and PAX2 expression has also been associated with SCOUTS and serous borderline tumours occurring in the fallopian tube (Laury et al., 2011). A relationship between discrete PAX2 gene dysregulation in the oviduct and both increasing age and, more significantly, the presence of co-existing serous cancer has been suggested (Quick et al., 2012). PAX2 appears to have both oncogenic and tumour suppressor gene roles in ovarian cancer cells, depending on the cellular context (Song et al., 2013). In chemoresistant epithelial ovarian cancer cell lines PAX2 expression was down regulated (Ju et al., 2009). In ovarian cancer cell lines inhibition of PAX2 led to reduced cell proliferation and apoptosis.
  
Entity Renal cell carcinoma
Note Renal cell carcinomas (RCC) cells express PAX2 (Gnarra and Dressler, 1995; Daniel et al., 2001; Igarashi et al., 2001) as a result of loss of the von-Hippel Lindau (VHL) tumour suppressor gene and hypoxia (Luu et al., 2009; reviewed in Kuroda et al., 2013). PAX2 promotes cell survival in renal cell carcinoma cells (Hueber et al., 2006). PAX2 expression correlates with proliferation index in the majority of kidney tumour subtypes, and expression levels are significantly higher as compared to primary RCCs in patients presenting with metastatic disease (Pan et al., 2013). PAX2 may therefore provide a useful prognostic marker for determining the severity of kidney cancers (Kuroda et al., 2013). PAX2 has been shown to regulate ADAM10, which is a metalloproteinase expressed in RCC cells. PAX2 has been validated in vivo as a therapeutic target for the treatment of renal cell carcinoma cells (Hueber et al., 2008). Immunogenic HLA-A*0201-binding T-cell epitopes of PAX2 have been identified, which were able to generate a T-cell response to at least 1 of 6 PAX2 peptide pools in patients with renal cell carcinoma, colorectal cancer, or lymphoma (Asemissen et al., 2009).
  
Entity Prostate cancer
Note PAX2 is expressed in prostate cancer cell lines and in some prostate cancer tissues (Khoubehi et al., 2001; Quick et al., 2010). During embryonic development in mice Pax2 mRNA levels are higher in the early stages of development than in postpubertal prostates (Chen Q et al., 2010). PAX2 may regulate the early, androgen-independent stages of prostate development, and expression is associated with a dorsally localized epithelial cell population retaining proliferative and differentiation potential, which may represent a subset of stem-like cells with characteristics of castrate-resistant prostate cancer cells (Chen Q et al., 2010). Angiotensin II up-regulates the expression of PAX2 in prostate cancer cells via the angiotensin II type I receptor (Bose et al., 2009b). Inhibition of PAX2 expression leads to cell death in prostate cancer cells, independently of p53 (Gibson et al., 2007). In addition, PAX2 expression represses the expression of human beta defensin-1 (hBD1) in prostate cancer cells, which may be a mechanism by which PAX2 helps to facilitate evasion of cancer cells from the immune system (Bose et al., 2009a). Human beta defensin is a component of the immune system linking innate and adaptive immune responses. Furthermore, PAX2 over-expression promotes the development of a metastatic state in prostate cancer cells, presumably through upregulating the expression of cell membrane proteins (Ueda et al., 2013).
  
Entity Nephrogenic adenoma
Note Nephrogenic adenoma is a benign lesion of the urinary tract, particularly of the urinary bladder. Immunostaining for PAX2 and PAX8 is useful in the detection of nephrogenic adenomas and particularly unveils those nephrogenic adenomas that have a flat pattern (Piña-Oviedo et al., 2013). PAX2 is expressed in bladder cancer cells, and inhibition of PAX2 expression in bladder cancer cell lines induces cell death, indicating a role for PAX2 in tumour cell survival (Muratovska et al., 2003).
  
Entity Wilms tumor
Note PAX2, as well as its closely related family member, PAX8, is expressed in Wilms tumor (Dressler and Douglass, 1992; Eccles et al., 1992), but neither PAX2 nor PAX8 is mutated in Wilms tumor (Tamimi et al., 2006). The gene encoding the calcineurin a-binding protein (CnABP) was identified as a novel target gene, which is up regulated by PAX2 (Nguyen et al., 2009), and is over-expressed in >70% of Wilms tumor samples analysed. CnABP was shown to promote cell proliferation and migration in cell culture experiments (Nguyen et al., 2009).
  
Entity Melanoma
Note PAX2 protein was expressed weakly in keratinocytes and melanocytes (Lee et al., 2011). Increased levels of PAX2 protein, as compared to melanocytes, were observed in some melanoma cell lines, and in some melanoma tissues, which strongly correlated with nuclear atypia and prominent nucleoli (i.e a more atypical cellular phenotype). PAX2 was found to regulate ADAM10 expression, which is a metalloproteinase with an important role in melanoma, and the silencing of PAX2 expression in melanoma cells abrogated chemoresistance, and anchorage-independent growth as well as decreasing migratory and invasive capacity of melanoma cells (Lee et al., 2011).
  
Entity Medulloblastoma
Note PAX2 is expressed in the majority of medulloblastomas, and its expression correlates with a less differentiated histology. Inhibition of PAX2 expression leads to apoptosis of medulloblastoma cells (Burger et al., 2012).
  
Entity Colorectal cancer
Note In colorectal cancers PAX2 protein is elevated due to decreased PHD3 expression (Yan et al., 2011). Silencing of PAX2 in colorectal cancer cells inhibits the activity of AP-1, a transcription factor that induces cyclin D1 expression (Zhang et al., 2012). PAX2 protein expression in colorectal cancer cells prevents JUNB from binding to c-jun and enhances phosphorylation of c-Jun (Zhang et al., 2012).
  
Entity Kaposi's sarcoma
Note PAX2 is expressed in Kaposi's sarcomas (Buttiglieri et al., 2004), where it induces apoptosis resistance and a proinvasive phenotype.
  
Entity Renal coloboma syndrome (RCS)
Note RCS is associated with heterozygous PAX2 mutations (Sanyanusin et al., 1995). RCS is characterised by end-stage renal failure and blindness (Eccles and Schimmenti, 1999; Bower et al., 2011). Increased apoptosis arises as a result of impaired PAX2 function, and is believed to be responsible for disrupted nephron formation (Porteous et al., 2000). Optic nerve defects are also observed in patients with RCS, and these lead to visual impairment (Eccles and Schimmenti, 1999). There are no reported instances of cancer in patients with renal-coloboma syndrome.
  
Entity Polycystic kidney disease
Note An aberrant persistent expression of PAX2 is implicated in autosomal dominant polycystic kidney disease, and cystogenesis is inhibited when Pax2 gene dosage is reduced in mice with ADPKD (Stayner et al., 2006; Eccles and Stayner, 2014). Similarly, in Cpk mice with recessive polycystic kidney disease, reduced dosage of the Pax2 gene was able to reduce cystogenesis, and also enhances apoptosis in fetal kidney cells (Ostrom et al., 2000).
  

External links

Nomenclature
HGNC (Hugo)PAX2   8616
Cards
AtlasPAX2ID41642ch10q24
Entrez_Gene (NCBI)PAX2  5076  paired box 2
GeneCards (Weizmann)PAX2
Ensembl (Hinxton)ENSG00000075891 [Gene_View]  chr10:102505468-102589698 [Contig_View]  PAX2 [Vega]
ICGC DataPortalENSG00000075891
AceView (NCBI)PAX2
Genatlas (Paris)PAX2
WikiGenes5076
SOURCE (Princeton)NM_000278 NM_003987 NM_003988 NM_003989 NM_003990
Genomic and cartography
GoldenPath (UCSC)PAX2  -  10q24.31   chr10:102505468-102589698 +  10q24.31   [Description]    (hg19-Feb_2009)
EnsemblPAX2 - 10q24.31 [CytoView]
Mapping of homologs : NCBIPAX2 [Mapview]
OMIM120330   167409   191830   
Gene and transcription
Genbank (Entrez)AY153483 AY153484 BC141452 BC148710 BM671839
RefSeq transcript (Entrez)NM_000278 NM_003987 NM_003988 NM_003989 NM_003990
RefSeq genomic (Entrez)AC_000142 NC_000010 NC_018921 NG_008680 NT_030059 NW_001838006 NW_004929376
Consensus coding sequences : CCDS (NCBI)PAX2
Cluster EST : UnigeneHs.155644 [ NCBI ]
CGAP (NCI)Hs.155644
Alternative Splicing : Fast-db (Paris)GSHG0003622
Alternative Splicing GalleryENSG00000075891
Gene ExpressionPAX2 [ NCBI-GEO ]     PAX2 [ SEEK ]   PAX2 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ02962 (Uniprot)
NextProtQ02962  [Medical]
With graphics : InterProQ02962
Splice isoforms : SwissVarQ02962 (Swissvar)
Domaine pattern : Prosite (Expaxy)PAIRED_1 (PS00034)    PAIRED_2 (PS51057)   
Domains : Interpro (EBI)Homeodomain-like    Paired_dom    Pax2_C    WHTH_DNA-bd_dom   
Related proteins : CluSTrQ02962
Domain families : Pfam (Sanger)PAX (PF00292)    Pax2_C (PF12403)   
Domain families : Pfam (NCBI)pfam00292    pfam12403   
Domain families : Smart (EMBL)PAX (SM00351)  
DMDM Disease mutations5076
Blocks (Seattle)Q02962
Human Protein AtlasENSG00000075891
Peptide AtlasQ02962
HPRD01330
IPIIPI00395548   IPI00220545   IPI00179609   IPI01026454   IPI01026240   IPI01026336   IPI00375136   IPI00872704   IPI00375134   
Protein Interaction databases
DIP (DOE-UCLA)Q02962
IntAct (EBI)Q02962
FunCoupENSG00000075891
BioGRIDPAX2
IntegromeDBPAX2
STRING (EMBL)PAX2
Ontologies - Pathways
QuickGOQ02962
Ontology : AmiGOnegative regulation of transcription from RNA polymerase II promoter  core promoter proximal region sequence-specific DNA binding  urogenital system development  branching involved in ureteric bud morphogenesis  branching involved in ureteric bud morphogenesis  cell fate determination  mesonephros development  neural tube closure  optic cup morphogenesis involved in camera-type eye development  mesenchymal to epithelial transition involved in metanephros morphogenesis  retinal pigment epithelium development  DNA binding  protein binding  nucleus  lysosome  microtubule organizing center  transcription, DNA-templated  transcription from RNA polymerase II promoter  axonogenesis  mesodermal cell fate specification  aging  visual perception  glial cell differentiation  superoxide-generating NADPH oxidase activity  optic nerve development  optic nerve morphogenesis  optic nerve structural organization  vestibulocochlear nerve formation  pancreas development  response to nutrient levels  protein-DNA complex  centriolar satellite  regulation of metanephros size  ureter maturation  pronephric field specification  inner ear morphogenesis  camera-type eye development  negative regulation of apoptotic process  negative regulation of apoptotic process  negative regulation of programmed cell death  negative regulation of cysteine-type endopeptidase activity involved in apoptotic process  protein complex  protein kinase B signaling  transcription regulatory region DNA binding  negative regulation of transcription, DNA-templated  positive regulation of transcription, DNA-templated  negative regulation of cytolysis  positive regulation of transcription from RNA polymerase II promoter  positive regulation of transcription from RNA polymerase II promoter  pronephros development  brain morphogenesis  stem cell differentiation  positive regulation of epithelial cell proliferation  oxidation-reduction process  oxidation-reduction process  mesenchymal to epithelial transition  paramesonephric duct development  optic chiasma development  cellular response to hydrogen peroxide  C2H2 zinc finger domain binding  cellular response to mechanical stimulus  cellular response to retinoic acid  cellular response to glucose stimulus  cellular response to epidermal growth factor stimulus  metanephric mesenchyme development  positive regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis  metanephric mesenchymal cell differentiation  mesonephric tubule formation  mesonephric duct development  nephric duct formation  ureter development  ureter morphogenesis  metanephric collecting duct development  metanephric epithelium development  metanephric distal convoluted tubule development  metanephric nephron tubule formation  positive regulation of metanephric glomerulus development  negative regulation of mesenchymal cell apoptotic process involved in metanephric nephron morphogenesis  regulation of metanephric nephron tubule epithelial cell differentiation  reactive oxygen species metabolic process  cochlea development  cochlea morphogenesis  positive regulation of branching involved in ureteric bud morphogenesis  negative regulation of mesenchymal cell apoptotic process involved in metanephros development  negative regulation of apoptotic process involved in metanephric collecting duct development  negative regulation of apoptotic process involved in metanephric nephron tubule development  negative regulation of reactive oxygen species metabolic process  positive regulation of metanephric DCT cell differentiation  positive regulation of optic nerve formation  
Ontology : EGO-EBInegative regulation of transcription from RNA polymerase II promoter  core promoter proximal region sequence-specific DNA binding  urogenital system development  branching involved in ureteric bud morphogenesis  branching involved in ureteric bud morphogenesis  cell fate determination  mesonephros development  neural tube closure  optic cup morphogenesis involved in camera-type eye development  mesenchymal to epithelial transition involved in metanephros morphogenesis  retinal pigment epithelium development  DNA binding  protein binding  nucleus  lysosome  microtubule organizing center  transcription, DNA-templated  transcription from RNA polymerase II promoter  axonogenesis  mesodermal cell fate specification  aging  visual perception  glial cell differentiation  superoxide-generating NADPH oxidase activity  optic nerve development  optic nerve morphogenesis  optic nerve structural organization  vestibulocochlear nerve formation  pancreas development  response to nutrient levels  protein-DNA complex  centriolar satellite  regulation of metanephros size  ureter maturation  pronephric field specification  inner ear morphogenesis  camera-type eye development  negative regulation of apoptotic process  negative regulation of apoptotic process  negative regulation of programmed cell death  negative regulation of cysteine-type endopeptidase activity involved in apoptotic process  protein complex  protein kinase B signaling  transcription regulatory region DNA binding  negative regulation of transcription, DNA-templated  positive regulation of transcription, DNA-templated  negative regulation of cytolysis  positive regulation of transcription from RNA polymerase II promoter  positive regulation of transcription from RNA polymerase II promoter  pronephros development  brain morphogenesis  stem cell differentiation  positive regulation of epithelial cell proliferation  oxidation-reduction process  oxidation-reduction process  mesenchymal to epithelial transition  paramesonephric duct development  optic chiasma development  cellular response to hydrogen peroxide  C2H2 zinc finger domain binding  cellular response to mechanical stimulus  cellular response to retinoic acid  cellular response to glucose stimulus  cellular response to epidermal growth factor stimulus  metanephric mesenchyme development  positive regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis  metanephric mesenchymal cell differentiation  mesonephric tubule formation  mesonephric duct development  nephric duct formation  ureter development  ureter morphogenesis  metanephric collecting duct development  metanephric epithelium development  metanephric distal convoluted tubule development  metanephric nephron tubule formation  positive regulation of metanephric glomerulus development  negative regulation of mesenchymal cell apoptotic process involved in metanephric nephron morphogenesis  regulation of metanephric nephron tubule epithelial cell differentiation  reactive oxygen species metabolic process  cochlea development  cochlea morphogenesis  positive regulation of branching involved in ureteric bud morphogenesis  negative regulation of mesenchymal cell apoptotic process involved in metanephros development  negative regulation of apoptotic process involved in metanephric collecting duct development  negative regulation of apoptotic process involved in metanephric nephron tubule development  negative regulation of reactive oxygen species metabolic process  positive regulation of metanephric DCT cell differentiation  positive regulation of optic nerve formation  
Protein Interaction DatabasePAX2
Wikipedia pathwaysPAX2
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)PAX2
SNP (GeneSNP Utah)PAX2
SNP : HGBasePAX2
Genetic variants : HAPMAPPAX2
1000_GenomesPAX2 
ICGC programENSG00000075891 
CONAN: Copy Number AnalysisPAX2 
Somatic Mutations in Cancer : COSMICPAX2 
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
LOVD (Leiden Open Variation Database)PAX2 variant database
DECIPHER (Syndromes)10:102505468-102589698
Mutations and Diseases : HGMDPAX2
OMIM120330    167409    191830   
MedgenPAX2
GENETestsPAX2
Disease Genetic AssociationPAX2
Huge Navigator PAX2 [HugePedia]  PAX2 [HugeCancerGEM]
Genomic VariantsPAX2  PAX2 [DGVbeta]
Exome VariantPAX2
dbVarPAX2
ClinVarPAX2
snp3D : Map Gene to Disease5076
General knowledge
Homologs : HomoloGenePAX2
Homology/Alignments : Family Browser (UCSC)PAX2
Phylogenetic Trees/Animal Genes : TreeFamPAX2
Chemical/Protein Interactions : CTD5076
Chemical/Pharm GKB GenePA32956
Clinical trialPAX2
Cancer Resource (Charite)ENSG00000075891
Other databases
Probes
Litterature
PubMed123 Pubmed reference(s) in Entrez
CoreMinePAX2
GoPubMedPAX2
iHOPPAX2

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PMID 1977574
 
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PMID 10466411
 
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PMID 11371938
 
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PMID 11850818
 
Ureteric bud apoptosis and renal hypoplasia in transgenic PAX2-Bax fetal mice mimics the renal-coloboma syndrome.
Dziarmaga A, Clark P, Stayner C, Julien JP, Torban E, Goodyer P, Eccles M.
J Am Soc Nephrol. 2003 Nov;14(11):2767-74.
PMID 14569086
 
Paired-Box genes are frequently expressed in cancer and often required for cancer cell survival.
Muratovska A, Zhou C, He S, Goodyer P, Eccles MR.
Oncogene. 2003 Sep 11;22(39):7989-97.
PMID 12970747
 
Gene expression patterns in ovarian carcinomas.
Schaner ME, Ross DT, Ciaravino G, Sorlie T, Troyanskaya O, Diehn M, Wang YC, Duran GE, Sikic TL, Caldeira S, Skomedal H, Tu IP, Hernandez-Boussard T, Johnson SW, O'Dwyer PJ, Fero MJ, Kristensen GB, Borresen-Dale AL, Hastie T, Tibshirani R, van de Rijn M, Teng NN, Longacre TA, Botstein D, Brown PO, Sikic BI.
Mol Biol Cell. 2003 Nov;14(11):4376-86. Epub 2003 Sep 5.
PMID 12960427
 
Role of Pax2 in apoptosis resistance and proinvasive phenotype of Kaposi's sarcoma cells.
Buttiglieri S, Deregibus MC, Bravo S, Cassoni P, Chiarle R, Bussolati B, Camussi G.
J Biol Chem. 2004 Feb 6;279(6):4136-43. Epub 2003 Nov 19.
PMID 14627715
 
Rescue of defective branching nephrogenesis in renal-coloboma syndrome by the caspase inhibitor, Z-VAD-fmk.
Clark P, Dziarmaga A, Eccles M, Goodyer P.
J Am Soc Nephrol. 2004 Feb;15(2):299-305.
PMID 14747376
 
Pax2 mutant mice display increased number and size of islets of Langerhans but no change in insulin and glucagon content.
Zaiko M, Estreicher A, Ritz-Laser B, Herrera P, Favor J, Meda P, Philippe J.
Eur J Endocrinol. 2004 Mar;150(3):389-95.
PMID 15012626
 
Pax2 expression occurs in renal medullary epithelial cells in vivo and in cell culture, is osmoregulated, and promotes osmotic tolerance.
Cai Q, Dmitrieva NI, Ferraris JD, Brooks HL, van Balkom BW, Burg M.
Proc Natl Acad Sci U S A. 2005 Jan 11;102(2):503-8. Epub 2004 Dec 27.
PMID 15623552
 
Hypomethylation-linked activation of PAX2 mediates tamoxifen-stimulated endometrial carcinogenesis.
Wu H, Chen Y, Liang J, Shi B, Wu G, Zhang Y, Wang D, Li R, Yi X, Zhang H, Sun L, Shang Y.
Nature. 2005 Dec 15;438(7070):981-7.
PMID 16355216
 
Suppression of ureteric bud apoptosis rescues nephron endowment and adult renal function in Pax2 mutant mice.
Dziarmaga A, Eccles M, Goodyer P.
J Am Soc Nephrol. 2006 Jun;17(6):1568-75. Epub 2006 May 3.
PMID 16672320
 
PAX2 inactivation enhances cisplatin-induced apoptosis in renal carcinoma cells.
Hueber PA, Waters P, Clark P, Eccles M, Goodyer P.
Kidney Int. 2006 Apr;69(7):1139-45.
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A PANorama of PAX genes in cancer and development.
Robson EJ, He SJ, Eccles MR.
Nat Rev Cancer. 2006 Jan;6(1):52-62. (REVIEW)
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Molecular mechanisms of oestrogen and SERMs in endometrial carcinogenesis.
Shang Y.
Nat Rev Cancer. 2006 May;6(5):360-8. (REVIEW)
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Pax2 gene dosage influences cystogenesis in autosomal dominant polycystic kidney disease.
Stayner C, Iglesias DM, Goodyer PR, Ellis L, Germino G, Zhou J, Eccles MR.
Hum Mol Genet. 2006 Dec 15;15(24):3520-8. Epub 2006 Nov 2.
PMID 17082250
 
Paired box genes, PAX-2 and PAX-8, are not frequently mutated in Wilms tumor.
Tamimi Y, Dietrich K, Stone K, Grundy P.
Mutat Res. 2006 Oct 10;601(1-2):46-50. Epub 2006 Jul 11.
PMID 16814811
 
PAX2 is reactivated in urinary tract obstruction and partially protects collecting duct cells from programmed cell death.
Cohen T, Loutochin O, Amin M, Capolicchio JP, Goodyer P, Jednak R.
Am J Physiol Renal Physiol. 2007 Apr;292(4):F1267-73. Epub 2006 Dec 12.
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Inhibition of PAX2 expression results in alternate cell death pathways in prostate cancer cells differing in p53 status.
Gibson W, Green A, Bullard RS, Eaddy AC, Donald CD.
Cancer Lett. 2007 Apr 18;248(2):251-61. Epub 2006 Sep 25.
PMID 16996682
 
Expression of PAX2 in papillary serous carcinoma of the ovary: immunohistochemical evidence of fallopian tube or secondary Mullerian system origin?
Tong GX, Chiriboga L, Hamele-Bena D, Borczuk AC.
Mod Pathol. 2007 Aug;20(8):856-63. Epub 2007 May 25.
PMID 17529925
 
Optic nerve axon number in mouse is regulated by PAX2.
Alur RP, Cox TA, Crawford MA, Gong X, Brooks BP.
J AAPOS. 2008 Apr;12(2):117-21. Epub 2007 Dec 21.
PMID 18083586
 
PAX2 expression by HHV-8-infected endothelial cells induced a proangiogenic and proinvasive phenotype.
Fonsato V, Buttiglieri S, Deregibus MC, Bussolati B, Caselli E, Di Luca D, Camussi G.
Blood. 2008 Mar 1;111(5):2806-15. Epub 2007 Dec 3.
PMID 18056486
 
In vivo validation of PAX2 as a target for renal cancer therapy.
Hueber PA, Iglesias D, Chu LL, Eccles M, Goodyer P.
Cancer Lett. 2008 Jun 28;265(1):148-55. doi: 10.1016/j.canlet.2008.02.016. Epub 2008 Apr 24.
PMID 18439754
 
Regulation of ERBB2 by oestrogen receptor-PAX2 determines response to tamoxifen.
Hurtado A, Holmes KA, Geistlinger TR, Hutcheson IR, Nicholson RI, Brown M, Jiang J, Howat WJ, Ali S, Carroll JS.
Nature. 2008 Dec 4;456(7222):663-6. doi: 10.1038/nature07483. Epub 2008 Nov 12.
PMID 19005469
 
Identification of an immunogenic HLA-A*0201-binding T-cell epitope of the transcription factor PAX2.
Asemissen AM, Haase D, Stevanovic S, Bauer S, Busse A, Thiel E, Rammensee HG, Keilholz U, Scheibenbogen C.
J Immunother. 2009 May;32(4):370-5. doi: 10.1097/CJI.0b013e31819d4e09.
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PAX2 oncogene negatively regulates the expression of the host defense peptide human beta defensin-1 in prostate cancer.
Bose SK, Gibson W, Bullard RS, Donald CD.
Mol Immunol. 2009a Mar;46(6):1140-8. doi: 10.1016/j.molimm.2008.11.004. Epub 2008 Dec 31.
PMID 19118900
 
Angiotensin II up-regulates PAX2 oncogene expression and activity in prostate cancer via the angiotensin II type I receptor.
Bose SK, Gibson W, Giri S, Nath N, Donald CD.
Prostate. 2009b Sep 1;69(12):1334-42. doi: 10.1002/pros.20980.
PMID 19517575
 
An intron 9 containing splice variant of PAX2.
Busse A, Rietz A, Schwartz S, Thiel E, Keilholz U.
J Transl Med. 2009 May 25;7:36. doi: 10.1186/1479-5876-7-36.
PMID 19467152
 
Identification of genes with differential expression in chemoresistant epithelial ovarian cancer using high-density oligonucleotide microarrays.
Ju W, Yoo BC, Kim IJ, Kim JW, Kim SC, Lee HP.
Oncol Res. 2009;18(2-3):47-56.
PMID 20066894
 
Expression of CD133, PAX2, ESA, and GPR30 in invasive ductal breast carcinomas.
Liu Q, Li JG, Zheng XY, Jin F, Dong HT.
Chin Med J (Engl). 2009 Nov 20;122(22):2763-9.
PMID 19951611
 
Loss of VHL and hypoxia provokes PAX2 up-regulation in clear cell renal cell carcinoma.
Luu VD, Boysen G, Struckmann K, Casagrande S, von Teichman A, Wild PJ, Sulser T, Schraml P, Moch H.
Clin Cancer Res. 2009 May 15;15(10):3297-304. doi: 10.1158/1078-0432.CCR-08-2779. Epub 2009 Apr 28.
PMID 19401348
 
Calcineurin a-binding protein, a novel modulator of the calcineurin-nuclear factor of activated T-cell signaling pathway, is overexpressed in wilms' tumors and promotes cell migration.
Nguyen AH, Beland M, Gaitan Y, Bouchard M.
Mol Cancer Res. 2009 Jun;7(6):821-31. doi: 10.1158/1541-7786.MCR-08-0402. Epub 2009 Jun 16.
PMID 19531566
 
PAX2 expression in low malignant potential ovarian tumors and low-grade ovarian serous carcinomas.
Tung CS, Mok SC, Tsang YT, Zu Z, Song H, Liu J, Deavers MT, Malpica A, Wolf JK, Lu KH, Gershenson DM, Wong KK.
Mod Pathol. 2009 Sep;22(9):1243-50. doi: 10.1038/modpathol.2009.92. Epub 2009 Jun 12.
PMID 19525924
 
Characterization of molecular and functional alterations of tumor endothelial cells to design anti-angiogenic strategies.
Bussolati B, Deregibus MC, Camussi G.
Curr Vasc Pharmacol. 2010 Mar;8(2):220-32. (REVIEW)
PMID 19485921
 
Secretory cell outgrowth, PAX2 and serous carcinogenesis in the Fallopian tube.
Chen EY, Mehra K, Mehrad M, Ning G, Miron A, Mutter GL, Monte N, Quade BJ, McKeon FD, Yassin Y, Xian W, Crum CP.
J Pathol. 2010 Sep;222(1):110-6. doi: 10.1002/path.2739.
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The developmental expression profile of PAX2 in the murine prostate.
Chen Q, DeGraff DJ, Sikes RA.
Prostate. 2010 May 1;70(6):654-65. doi: 10.1002/pros.21099.
PMID 20017165
 
MCF-7 breast cancer cells selected for tamoxifen resistance acquire new phenotypes differing in DNA content, phospho-HER2 and PAX2 expression, and rapamycin sensitivity.
Leung E, Kannan N, Krissansen GW, Findlay MP, Baguley BC.
Cancer Biol Ther. 2010 May 1;9(9):717-24.
PMID 20234184
 
Joint loss of PAX2 and PTEN expression in endometrial precancers and cancer.
Monte NM, Webster KA, Neuberg D, Dressler GR, Mutter GL.
Cancer Res. 2010 Aug 1;70(15):6225-32. doi: 10.1158/0008-5472.CAN-10-0149. Epub 2010 Jul 14.
PMID 20631067
 
The distribution of PAX-2 immunoreactivity in the prostate gland, seminal vesicle, and ejaculatory duct: comparison with prostatic adenocarcinoma and discussion of prostatic zonal embryogenesis.
Quick CM, Gokden N, Sangoi AR, Brooks JD, McKenney JK.
Hum Pathol. 2010 Aug;41(8):1145-9. doi: 10.1016/j.humpath.2010.01.010. Epub 2010 Apr 22.
PMID 20413145
 
High-grade fimbrial-ovarian carcinomas are unified by altered p53, PTEN and PAX2 expression.
Roh MH, Yassin Y, Miron A, Mehra KK, Mehrad M, Monte NM, Mutter GL, Nucci MR, Ning G, Mckeon FD, Hirsch MS, Wa X, Crum CP.
Mod Pathol. 2010 Oct;23(10):1316-24. doi: 10.1038/modpathol.2010.119. Epub 2010 Jun 18.
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PAX2 is activated by estradiol in breast cancer cells of the luminal subgroup selectively, to confer a low invasive phenotype.
Beauchemin D, Lacombe C, Van Themsche C.
Mol Cancer. 2011 Dec 14;10:148. doi: 10.1186/1476-4598-10-148.
PMID 22168360
 
Clinical utility gene card for: renal coloboma (Papillorenal) syndrome.
Bower M, Eccles M, Heidet L, Schimmenti LA.
Eur J Hum Genet. 2011 Sep;19(9). doi: 10.1038/ejhg.2011.16. Epub 2011 Feb 16.
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The transcription factor PAX2 regulates ADAM10 expression in renal cell carcinoma.
Doberstein K, Pfeilschifter J, Gutwein P.
Carcinogenesis. 2011 Nov;32(11):1713-23. doi: 10.1093/carcin/bgr195. Epub 2011 Aug 30.
PMID 21880579
 
Caution in metastatic renal cell carcinoma within lymph nodes: PAX-2 expression is also seen in nodal lymphocytes.
Gilmore L, Dewar R.
Arch Pathol Lab Med. 2011 Apr;135(4):414; author reply 414-5. doi: 10.1043/2010-0531-LE.1.
PMID 21466350
 
Fallopian tube correlates of ovarian serous borderline tumors.
Laury AR, Ning G, Quick CM, Bijron J, Parast MM, Betensky RA, Vargas SO, McKeon FD, Xian W, Nucci MR, Crum CP.
Am J Surg Pathol. 2011 Dec;35(12):1759-65. doi: 10.1097/PAS.0b013e318233b0f7.
PMID 22089527
 
PAX2 regulates ADAM10 expression and mediates anchorage-independent cell growth of melanoma cells.
Lee SB, Doberstein K, Baumgarten P, Wieland A, Ungerer C, Burger C, Hardt K, Boehncke WH, Pfeilschifter J, Mihic-Probst D, Mittelbronn M, Gutwein P.
PLoS One. 2011;6(8):e22312. doi: 10.1371/journal.pone.0022312. Epub 2011 Aug 18.
PMID 21876729
 
Prolyl hydroxylase domain protein 3 targets Pax2 for destruction.
Yan B, Jiao S, Zhang HS, Lv DD, Xue J, Fan L, Wu GH, Fang J.
Biochem Biophys Res Commun. 2011 Jun 3;409(2):315-20. doi: 10.1016/j.bbrc.2011.05.012. Epub 2011 May 14.
PMID 21575608
 
RNA interference of pax2 inhibits growth of transplanted human endometrial cancer cells in nude mice.
Zhang LP, Shi XY, Zhao CY, Liu YZ, Cheng P.
Chin J Cancer. 2011 Jun;30(6):400-6.
PMID 21627862
 
PAX2 loss by immunohistochemistry occurs early and often in endometrial hyperplasia.
Allison KH, Upson K, Reed SD, Jordan CD, Newton KM, Doherty J, Swisher EM, Garcia RL.
Int J Gynecol Pathol. 2012 Mar;31(2):151-159. doi: 10.1097/PGP.0b013e318226b376.
PMID 22317873
 
Update of PAX2 mutations in renal coloboma syndrome and establishment of a locus-specific database.
Bower M, Salomon R, Allanson J, Antignac C, Benedicenti F, Benetti E, Binenbaum G, Jensen UB, Cochat P, DeCramer S, Dixon J, Drouin R, Falk MJ, Feret H, Gise R, Hunter A, Johnson K, Kumar R, Lavocat MP, Martin L, Moriniere V, Mowat D, Murer L, Nguyen HT, Peretz-Amit G, Pierce E, Place E, Rodig N, Salerno A, Sastry S, Sato T, Sayer JA, Schaafsma GC, Shoemaker L, Stockton DW, Tan WH, Tenconi R, Vanhille P, Vats A, Wang X, Warman B, Weleber RG, White SM, Wilson-Brackett C, Zand DJ, Eccles M, Schimmenti LA, Heidet L.
Hum Mutat. 2012 Mar;33(3):457-66. doi: 10.1002/humu.22020. Epub 2012 Jan 31.
PMID 22213154
 
PAX2 is an antiapoptotic molecule with deregulated expression in medulloblastoma.
Burger MC, Brucker DP, Baumgarten P, Ronellenfitsch MW, Wanka C, Hasselblatt M, Eccles MR, Klingebiel T, Weller M, Rieger J, Mittelbronn M, Steinbach JP.
Int J Oncol. 2012 Jul;41(1):235-41. doi: 10.3892/ijo.2012.1446. Epub 2012 Apr 25.
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PAX Genes in Cancer; Friends or Foes?
Li CG, Eccles MR.
Front Genet. 2012 Jan 31;3:6. doi: 10.3389/fgene.2012.00006. eCollection 2012.
PMID 22303411
 
PAX2-null secretory cell outgrowths in the oviduct and their relationship to pelvic serous cancer.
Quick CM, Ning G, Bijron J, Laury A, Wei TS, Chen EY, Vargas SO, Betensky RA, McKeon FD, Xian W, Crum CP.
Mod Pathol. 2012 Mar;25(3):449-55. doi: 10.1038/modpathol.2011.175. Epub 2011 Nov 11.
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PAX2 protein induces expression of cyclin D1 through activating AP-1 protein and promotes proliferation of colon cancer cells.
Zhang HS, Yan B, Li XB, Fan L, Zhang YF, Wu GH, Li M, Fang J.
J Biol Chem. 2012 Dec 28;287(53):44164-72. doi: 10.1074/jbc.M112.401521. Epub 2012 Nov 7.
PMID 23135283
 
The life and times of low-grade serous carcinoma of the ovary.
Gershenson DM.
Am Soc Clin Oncol Educ Book. 2013. doi: 10.1200/EdBook_AM.2013.33.e195.
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Recent advances of immunohistochemistry for diagnosis of renal tumors.
Kuroda N, Tanaka A, Ohe C, Nagashima Y.
Pathol Int. 2013 Aug;63(8):381-90. doi: 10.1111/pin.12080. (REVIEW)
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Significant variation of immunohistochemical marker expression in paired primary and metastatic clear cell renal cell carcinomas.
Pan Z, Grizzle W, Hameed O.
Am J Clin Pathol. 2013 Sep;140(3):410-8. doi: 10.1309/AJCP8DMPEIMVH6YP.
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Flat pattern of nephrogenic adenoma: previously unrecognized pattern unveiled using PAX2 and PAX8 immunohistochemistry.
Pina-Oviedo S, Shen SS, Truong LD, Ayala AG, Ro JY.
Mod Pathol. 2013 Jun;26(6):792-8. doi: 10.1038/modpathol.2012.239. Epub 2013 Jan 18.
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PAX2 Expression in Ovarian Cancer.
Song H, Kwan SY, Izaguirre DI, Zu Z, Tsang YT, Tung CS, King ER, Mok SC, Gershenson DM, Wong KK.
Int J Mol Sci. 2013 Mar 15;14(3):6090-105. doi: 10.3390/ijms14036090.
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Hyper-expression of PAX2 in human metastatic prostate tumors and its role as a cancer promoter in an in vitro invasion model.
Ueda T, Ito S, Shiraishi T, Kulkarni P, Ueno A, Nakagawa H, Kimura Y, Hongo F, Kamoi K, Kawauchi A, Miki T.
Prostate. 2013 Sep;73(13):1403-12. doi: 10.1002/pros.22687. Epub 2013 Jun 14.
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Polycystic kidney disease - where gene dosage counts.
Eccles MR, Stayner CA.
F1000Prime Rep. 2014 Apr 1;6:24. doi: 10.12703/P6-24. eCollection 2014. (REVIEW)
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Contributor(s)

Written07-2005Ewan Robson, Jess Whall, Michael Eccles
Developmental Genetics Group, Department of Pathology, University of Otago, PO Box 913,Dunedin 9015, New Zealand
Updated08-2014Michael Eccles
Department of Pathology, Dunedin School of Medicine, University of Otago, PO Box 913, Dunedin, 9054, New Zealand

Citation

This paper should be referenced as such :
Eccles M
PAX2 (Paired box gene 2);
Atlas Genet Cytogenet Oncol Haematol. August 2014
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Atlas Genet Cytogenet Oncol Haematol. August 2014
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