Atlas of Genetics and Cytogenetics in Oncology and Haematology

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AREG (amphiregulin (schwannoma-derived growth factor))

Identity

Other namesAR
CRDGF
MGC13647
OTTHUMP00000160473
SDGF
amphiregulin
HGNC (Hugo) AREG
LocusID (NCBI) 374
Location 4q13.3
Location_base_pair Starts at 75310853 and ends at 75320726 bp from pter ( according to hg19-Feb_2009)  [Mapping]

DNA/RNA

 
  Figure 2: Map of the human AR gene showing the exon organization and protein domains. The gene is drawn to scale in a 5'-to-3' orientation. Intron lengths in kilobase pairs are indicated between each exon. The six exons are shown, with the length in base pairs being listed directly under each exon. The corresponding position of each exon about the AR mRNA is shown below. Protein domains are represented by shaded boxes. The number of amino acid residues in each domain is indicated. The two dark filled boxes represent hydrophobic stretches that correspond to the signal peptide and transmembrane (TM) domains. Mature AR is represented by two boxes, the N-terminal hydrophilic heparin-binding domain and the C-terminal EGF-like motif (from Plowman et al., 1990).
Description The AR/AREG human gene spans 10kb in the genomic DNA and it is composed of six exons.
Transcription The transcription of the AR gene produces a 1.4 kb mRNA. AR gene shows broad constitutive expression, being more prevalent in human ovary and placenta although it is also expressed in pancreas, cardiac muscle, testis, colon, breast, lung, spleen and kidney, whereas it is undetectable in liver.

Protein

 
  AR is synthesized as a membrane-anchored precursor (Pro-AR) of 252 amino acids. Pro-AR encompasses a signal peptide, a Pro-region, a heparin-binding domain, an EGF-like domain, a transmembrane region (TM) and a carboxy-terminal cytosolic tail (CT-tail). The nuclear localization signal (NLS) and glycosylation sites are indicated.
Description AR is synthesized as a 252-amino acids transmembrane glycoprotein, also known as transmembrane precursor or pro-form (Pro-AR). Pro-AR consists of a hydrophilic extracellular N-terminus (or ectodomain), a hydrophobic transmembrane domain (TM) and a hydrophilic cytoplasmic C-terminus (CT-tail). In the extracellular N-terminus we can distinguish an N-terminal pro-region containing glycosylation sites followed by a heparin-binding domain and an epidermal growth factor EGF-like region. The EGF-like region is shared by other members of the EGF family of ligands. At the plasma membrane Pro-AR undergoes proteolytic cleavage to release the mature soluble factor in a process known as "ectodomain shedding". Cleavage of Pro-AR at two N-terminal sites gives rise to two major soluble forms of ~19 and ~21 kDa. Alternatively Pro-AR cleavage can produce a larger 43-kDa soluble protein corresponding to the entire extracellular domain. Cleavage of Pro-AR at the cell surface can be mediated by tumor necrosis factor-alpha converting enzyme (TACE), a member of the disintegrin and metalloproteinase (ADAM) family also known as ADAM17. Shedding of AR allows the autocrine or paracrine interaction of the mature ligand with its cognate receptor, the EGFR (also known as ErbB1), a transmembrane protein endowed with tyrosine kinase activity, although juxtacine interaction between membrane-bound Pro-AR and the EGFR has also been observed.
Expression AR is constitutively expressed in human ovary and placenta, in pancreas, cardiac muscle, testis, colon, breast, lung, spleen and kidney, whereas it is undetectable in liver. AR gene overexpression has been frequently demonstrated in cancerous tissues like colon, breast, bladder, prostate, pancreas, lung, ovary, squamous cell carcinomas, hepatocarcinoma and myeloma cells. Besides changes in AR gene expression, different stimuli can also influence the availability of this growth factor through the stimulation of Pro-AR cleavage at the cell membrane. This is achieved by the activation of TACE/ADAM17 in response to agonists acting through G-proteins coupled receptors (GPCRs) in a process termed EGFR transactivation.
Localisation AR is synthesized as a transmembrane precursor which is proteolytically cleaved to produce the soluble factor.
Function Binding of AR to the epidermal growth factor receptor (EGFR/ErbB1) triggers key intracellular signaling pathways, such as the mitogenic MAPK and survival PI3K/Akt pathways, which have been demonstrated to participate in the transduction of AR-effects. AR was originally identified as a factor capable of inhibiting the growth of certain carcinoma cell lines, while stimulating the proliferation of normal cells, a fact that motivated its denomination. Actually, depending on its concentration and the nature of the target cell AR promotes the growth and survival of most cell types, both normal and transformed.
 
  Figure 4: Cladogram
Figure 5: from Sanderson et al., 2006.
Homology The EGF-like region characterized by a six-cysteine consensus motif, XnCX7CX4-5CX10CXCX5GX2CXn is shared by other members of the EGF family of ligands.
Mature HB-EGF and AR also have N-terminal extensions, composed of predominantly basic residues which are thought to confer their heparin-binding abilities.

Implicated in

Entity Various cancers
Note AR gene overexpression has been demonstrated in a large variety of human cancerous tissues such as colon, breast, liver, prostate, pancreas, lung, squamous cell carcinoma, bladder, ovary, skin and myeloma cells. The genetic or epigenetic alterations responsible for this overexpression are unknown. However it has been documented that the expression of AR can be induced by hormones such as androgen or 17beta-estradiol, EGF-family growth factors, such as TGF-alpha or AR itself, pro-inflammatory cytokines, such as TNF-alpha or interleukin-1 beta, prostaglandins, aryl hydrocarbon receptor agonists, bile acids, or hypoxic conditions.
In addition to these changes in AR gene expression the availability of this growth factor may be increased through the stimulation of pro-AR cleavage at the cell membrane, which result in a process termed EGFR transactivation. This is achieved through the activation of TACE/ADAM17 in response to agonists acting through GPCRs. This process has been shown in different cancer cells upon treatment with lysophosphatidic acid, gastrin-releasing peptide, cigarette smoke, or the activation of cannabinoid receptors.
In vitro studies performed in tumour cell lines upon treatment with AR, or conversely with specific siRNAs to silence AR gene expression, have shown that AR plays an important role in the proliferation and survival of transformed cells. These assays have also demonstrated that AR participates in the maintenance of the metastatic and oncogenic properties of these cells as well as in their resistance to chemotherapy.
The role of AR in cancer development and progression is also supported by clinical data. It has been established a significant correlation between elevated AR mRNA levels in bladder tumour tissue and poor patient survival. In patients with advanced non-squamous non-small cell lung cancers increased levels of circulating AR in serum are predictors of poor response to gefitinib.
  
Entity Psoriasis
Note AR is an autocrine growth factor for keratinocytes and the expression of AR is significantly induced in psoriatic epidermis. Transgenic mice which overexpress AR in the epidermis develop a psoriasis-like cutaneous phenotype and psoriatic arthritis. These results show that AR contributes to the pathogenesis of psoriasis and present AR as a target for anti-psoriatic therapy. Indeed the use of heparin, which binds and inhibits AR activity or the administration of glucosamine which induces the synthesis of heparan sulfates, physiological AR antagonists, provide therapeutic benefits in psoriasis.
  
Entity Rheumatoid arthritis
Note The expression of AR is increased in rheumatoid arthritis patients. AR induces the proliferation of fibroblast-like synoviocytes and the production of proinflammatory cytokines such as interleukin-8 and vascular endothelial growth factor.
  

External links

Nomenclature
HGNC (Hugo)AREG   651
Entrez_Gene (NCBI)AREG  374  amphiregulin
Cards
AtlasAREGID690ch4q13
GeneCards (Weizmann)AREG
Ensembl (Hinxton)ENSG00000109321 [Gene_View]  chr4:75310853-75320726 [Contig_View]  AREG [Vega]
AceView (NCBI)AREG
Genatlas (Paris)AREG
euGene (Indiana)374
SOURCE (Stanford)NM_001657
Genomic and cartography
GoldenPath (UCSC)AREG  -  4q13.3   chr4:75310853-75320726 +  4q13-q21   [Description]    (hg19-Feb_2009)
EnsemblAREG - 4q13-q21 [CytoView]
Mapping of homologs : NCBIAREG [Mapview]
OMIM104640   
Gene and transcription
Genbank (Entrez)BC009799 BC146953 BC146967 BT019866 DQ892890
RefSeq transcript (SRS)NM_001657
RefSeq transcript (Entrez)NM_001657
RefSeq genomic (SRS)AC_000136 NC_000004 NT_022778 NW_001838914
RefSeq genomic (Entrez)AC_000136 NC_000004 NT_022778 NW_001838914
Consensus coding sequences : CCDS (NCBI)AREG
Cluster EST : UnigeneHs.270833 [ SRS ] Hs.270833 [ NCBI ]
Alternative Splicing : Fast-db (Paris)5642
Alternative Splicing GalleryENSG00000109321
Gene ExpressionAREG [ NCBI-GEO ]   AREG [ EBI - ARRAY_EXPRESS ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP15514 (SRS) P15514 (Uniprot)
With graphics : InterProP15514
Splice isoforms : SwissVarP15514(Swissvar)
Domaine pattern : Prosite (SRS)EGF_1 (PS00022)    EGF_2 (PS01186)    EGF_3 (PS50026)   
Domaine pattern : Prosite (Expaxy)EGF_1 (PS00022)    EGF_2 (PS01186)    EGF_3 (PS50026)   
Domains : Interpro (SRS)EG-like_dom    EGF-like    EGF-like_reg_CS    EGF_rcpt_ligand   
Domains : Interpro (EBI)EG-like_dom    EGF-like    EGF-like_reg_CS    EGF_rcpt_ligand   
Related proteins : CluSTrP15514
Domain families : Pfam (SRS)
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Domain families : Smart (EMBL)EGF (SM00181)  
Blocks (Seattle)P15514
PDB (SRS)2RNL   
PDB (PDBSum)2RNL   
PDB (IMB)2RNL   
PDB (RSDB)2RNL   
Human Protein AtlasENSG00000109321
HPRD00093
IPIIPI00012023   IPI00965669   
Protein Interaction databases
DIP (DOE-UCLA)P15514
IntAct (EBI)P15514
FunCoupENSG00000109321
REACTOMEAREG
BioGRIDAREG
InParanoidP15514
Interologous Interaction database P15514
Polymorphism : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)AREG
SNP (GeneSNP Utah)AREG
SNP : HGBaseAREG
Genetic variants : HAPMAPAREG
Somatic Mutations in Cancer : COSMICAREG 
CONAN: Copy Number AnalysisAREG 
Mutations and Diseases : HGMDAREG
OMIM104640   
GENETests104640   
Disease Genetic AssociationAREG
Huge Navigator AREG [HugePedia]  AREG [HugeCancerGEM]
Genomic VariantsAREG
snp3D : Map Gene to Disease374
General knowledge
Homologs : HomoloGeneAREG
Homology/Alignments : Family Browser (UCSC)AREG
Phylogenetic Trees/Animal Genes : TreeFamAREG
Chemical/Protein Interactions : CTD374
Chemical/Pharm GKB GenePA24933
Clinical trialAREG
Cancer Resource (Charite)ENSG00000109321
Ontology : AmiGO
Ontology : EGO-EBI
Other databases
Probes
Probes : ImagenesAREG Related clones (RZPD - Berlin)
Litterature
PubMed91 Pubmed reference(s) in Entrez
PubGeneAREG
iHOPAREG

Bibliography

Amphiregulin: a bifunctional growth-modulating glycoprotein produced by the phorbol 12-myristate 13-acetate-treated human breast adenocarcinoma cell line MCF-7.
Shoyab M, McDonald VL, Bradley JG, Todaro GJ.
Proc Natl Acad Sci U S A. 1988 Sep;85(17):6528-32.
PMID 3413110
 
Structure and function of human amphiregulin: a member of the epidermal growth factor family.
Shoyab M, Plowman GD, McDonald VL, Bradley JG, Todaro GJ.
Science. 1989 Feb 24;243(4894 Pt 1):1074-6.
PMID 2466334
 
Structure, expression and function of a schwannoma-derived growth factor.
Kimura H, Fischer WH, Schubert D.
Nature. 1990 Nov 15;348(6298):257-60.
PMID 2234093
 
The amphiregulin gene encodes a novel epidermal growth factor-related protein with tumor-inhibitory activity.
Plowman GD, Green JM, McDonald VL, Neubauer MG, Disteche CM, Todaro GJ, Shoyab M.
Mol Cell Biol. 1990 May;10(5):1969-81.
PMID 2325643
 
A heparin sulfate-regulated human keratinocyte autocrine factor is similar or identical to amphiregulin.
Cook PW, Mattox PA, Keeble WW, Pittelkow MR, Plowman GD, Shoyab M, Adelman JP, Shipley GD.
Mol Cell Biol. 1991 May;11(5):2547-57.
PMID 2017164
 
Response to and expression of amphiregulin by ovarian carcinoma and normal ovarian surface epithelial cells: nuclear localization of endogenous amphiregulin.
Johnson GR, Saeki T, Auersperg N, Gordon AW, Shoyab M, Salomon DS, Stromberg K.
Biochem Biophys Res Commun. 1991 Oct 31;180(2):481-8.
PMID 1953719
 
Amphiregulin messenger RNA is elevated in psoriatic epidermis and gastrointestinal carcinomas.
Cook PW, Pittelkow MR, Keeble WW, Graves-Deal R, Coffey RJ Jr, Shipley GD.
Cancer Res. 1992 Jun 1;52(11):3224-7.
PMID 1591731
 
Colorectum cell-derived growth factor (CRDGF) is homologous to amphiregulin, a member of the epidermal growth factor family.
Culouscou JM, Remacle-Bonnet M, Carlton GW, Plowman GD, Shoyab M.
Growth Factors. 1992;7(3):195-205.
PMID 1333777
 
Amphiregulin induces tyrosine phosphorylation of the epidermal growth factor receptor and p185erbB2. Evidence that amphiregulin acts exclusively through the epidermal growth factor receptor at the surface of human epithelial cells.
Johnson GR, Kannan B, Shoyab M, Stromberg K.
J Biol Chem. 1993 Feb 5;268(4):2924-31.
PMID 7679104
 
Characterization of high and low molecular weight forms of amphiregulin that differ in glycosylation and peptide core length. Evidence that the NH2-terminal region is not critical for bioactivity.
Johnson GR, Prigent SA, Gullick WJ, Stromberg K.
J Biol Chem. 1993 Sep 5;268(25):18835-43.
PMID 8360173
 
Expression of amphiregulin, a novel gene of the epidermal growth factor family, in human gastric carcinomas.
Kitadai Y, Yasui W, Yokozaki H, Kuniyasu H, Ayhan A, Haruma K, Kajiyama G, Johnson GR, Tahara E.
Jpn J Cancer Res. 1993 Aug;84(8):879-84.
PMID 8407551
 
Induction and expression of amphiregulin in human pancreatic cancer.
Ebert M, Yokoyama M, Kobrin MS, Friess H, Lopez ME, Buchler MW, Johnson GR, Korc M.
Cancer Res. 1994 Aug 1;54(15):3959-62.
PMID 8033121
 
Heparan sulfate is essential to amphiregulin-induced mitogenic signaling by the epidermal growth factor receptor.
Johnson GR, Wong L.
J Biol Chem. 1994 Oct 28;269(43):27149-54.
PMID 7929459
 
The heparin-binding domain of amphiregulin necessitates the precursor pro-region for growth factor secretion.
Thorne BA, Plowman GD.
Mol Cell Biol. 1994 Mar;14(3):1635-46.
PMID 8114701
 
Epidermal growth factor-related peptides and their relevance to gastrointestinal pathophysiology.
Barnard JA, Beauchamp RD, Russell WE, Dubois RN, Coffey RJ.
Gastroenterology. 1995 Feb;108(2):564-80. (REVIEW)
PMID 7835600
 
Schwannoma-derived growth factor interacts with the epidermal growth factor receptor.
Maher PA, Schubert D.
J Neurochem. 1995 Oct;65(4):1895-8.
PMID 7561890
 
The role of amphiregulin in breast cancer.
Salomon DS, Normanno N, Ciardiello F, Brandt R, Shoyab M, Todaro GJ.
Breast Cancer Res Treat. 1995;33(2):103-14. (REVIEW)
PMID 7749138
 
Induction of anchorage-independent growth by amphiregulin
Adam RM, Chamberlin SG, Davies DE.
Growth Factors. 1996;13(3-4):193-203.
PMID 8919027
 
Co-expression of heparin-binding EGF-like growth factor and related peptides in human gastric carcinoma.
Naef M, Yokoyama M, Friess H, Buchler MW, Korc M.
Int J Cancer. 1996 May 3;66(3):315-21.
PMID 8621250
 
Overexpression of amphiregulin, a major autocrine growth factor for cultured human keratinocytes, in hyperproliferative skin diseases.
Piepkorn M.
Am J Dermatopathol. 1996 Apr;18(2):165-71.
PMID 8739992
 
Transgenic expression of the human amphiregulin gene induces a psoriasis-like phenotype.
Cook PW, Piepkorn M, Clegg CH, Plowman GD, DeMay JM, Brown JR, Pittelkow MR.
J Clin Invest. 1997 Nov 1;100(9):2286-94.
PMID 9410906
 
Anti-sense oligonucleotides directed against EGF-related growth factors enhance anti-proliferative effect of conventional anti-tumor drugs in human colon-cancer cells.
De Luca A, Selvam MP, Sandomenico C, Pepe S, Bianco AR, Ciardiello F, Salomon DS, Normanno N.
Int J Cancer. 1997 Oct 9;73(2):277-82.
PMID 9335455
 
Glucosamine for psoriasis?
McCarty MF.
Med Hypotheses. 1997 May;48(5):437-41.
PMID 9185133
 
Cell surface ectodomain cleavage of human amphiregulin precursor is sensitive to a metalloprotease inhibitor. Release of a predominant N-glycosylated 43-kDa soluble form.
Brown CL, Meise KS, Plowman GD, Coffey RJ, Dempsey PJ.
J Biol Chem. 1998 Jul 3;273(27):17258-68.
PMID 9642297
 
Growth control mechanisms in normal and transformed intestinal cells.
Burgess AW.
Philos Trans R Soc Lond B Biol Sci. 1998 Jun 29;353(1370):903-9. (REVIEW)
PMID 9684287
 
Evaluation of epidermal growth factor-related growth factors and receptors and of neoangiogenesis in completely resected stage I-IIIA non-small-cell lung cancer: amphiregulin and microvessel count are independent prognostic indicators of survival.
Fontanini G, De Laurentiis M, Vignati S, Chine S, Lucchi M, Silvestri V, Mussi A, De Placido S, Tortora G, Bianco AR, Gullick W, Angeletti CA, Bevilacqua G, Ciardiello F.
Clin Cancer Res. 1998 Jan;4(1):241-9.
PMID 9516978
 
Overexpression of amphiregulin in the epidermis of transgenic mice induces a psoriasis-like cutaneous phenotype.
Cook PW, Pittelkow MR, Piepkorn M.
J Invest Dermatol. 1999 Nov;113(5):860.
PMID 10571748
 
Expression of cripto and amphiregulin in colon mucosa from high risk colon cancer families.
De Angelis E, Grassi M, Gullick WJ, Johnson GR, Rossi GB, Tempesta A, De Angelis F, De Luca A, Salomon DS, Normanno N.
Int J Oncol. 1999 Mar;14(3):437-40.
PMID 10024674
 
Metalloprotease-mediated ligand release regulates autocrine signaling through the epidermal growth factor receptor.
Dong J, Opresko LK, Dempsey PJ, Lauffenburger DA, Coffey RJ, Wiley HS.
Proc Natl Acad Sci U S A. 1999 May 25;96(11):6235-40.
PMID 10339571
 
The Wilms tumor suppressor WT1 encodes a transcriptional activator of amphiregulin.
Lee SB, Huang K, Palmer R, Truong VB, Herzlinger D, Kolquist KA, Wong J, Paulding C, Yoon SK, Gerald W, Oliner JD, Haber DA.
Cell. 1999 Sep 3;98(5):663-73.
PMID 10490105
 
Antisense expression for amphiregulin suppresses tumorigenicity of a transformed human breast epithelial cell line.
Ma L, Gauville C, Berthois Y, Millot G, Johnson GR, Calvo F.
Oncogene. 1999 Nov 11;18(47):6513-20.
PMID 10597254
 
Preneoplastic mammary tumor markers: Cripto and Amphiregulin are overexpressed in hyperplastic stages of tumor progression in transgenic mice.
Niemeyer CC, Spencer-Dene B, Wu JX, Adamson ED.
Int J Cancer. 1999 May 17;81(4):588-91.
PMID 10225449
 
Simultaneous blockage of different EGF-like growth factors results in efficient growth inhibition of human colon carcinoma xenografts.
De Luca A, Arra C, D'Antonio A, Casamassimi A, Losito S, Ferraro P, Ciardiello F, Salomon DS, Normanno N.
Oncogene. 2000 Nov 30;19(51):5863-71.
PMID 11127817
 
Regulation of keratinocyte function by growth factors.
Hashimoto K.
J Dermatol Sci. 2000 Dec;24 Suppl 1:S46-50. (REVIEW)
PMID 11137396
 
The proamphiregulin cytoplasmic domain is required for basolateral sorting, but is not essential for constitutive or stimulus-induced processing in polarized Madin-Darby canine kidney cells.
Brown CL, Coffey RJ, Dempsey PJ.
J Biol Chem. 2001 Aug 3;276(31):29538-49. Epub 2001 May 29.
PMID 11382759
 
Transforming growth factor alpha, amphiregulin and cripto-1 are frequently expressed in advanced human ovarian carcinomas.
D'Antonio A, Losito S, Pignata S, Grassi M, Perrone F, De Luca A, Tambaro R, Bianco C, Gullick WJ, Johnson GR, Iaffaioli VR, Salomon DS, Normanno N.
Int J Oncol. 2002 Nov;21(5):941-8.
PMID 12370739
 
New strategy for antedrug application: development of metalloproteinase inhibitors as antipsoriatic drugs.
Sawa M, Tsukamoto T, Kiyoi T, Kurokawa K, Nakajima F, Nakada Y, Yokota K, Inoue Y, Kondo H, Yoshino K.
J Med Chem. 2002 Feb 14;45(4):930-6.
PMID 11831905
 
Prognostic value of ERBB family mRNA expression in breast carcinomas.
Bieche I, Onody P, Tozlu S, Driouch K, Vidaud M, Lidereau R.
Int J Cancer. 2003 Sep 20;106(5):758-65.
PMID 12866037
 
Amphiregulin overexpression results in rapidly growing keratinocytic tumors: an in vivo xenograft model of keratoacanthoma.
Billings SD, Southall MD, Li T, Cook PW, Baldridge L, Moores WB, Spandau DF, Foley JG, Travers JB.
Am J Pathol. 2003 Dec;163(6):2451-8.
PMID 14633617
 
TACE/ADAM17 processing of EGFR ligands indicates a role as a physiological convertase.
Lee DC, Sunnarborg SW, Hinkle CL, Myers TJ, Stevenson MY, Russell WE, Castner BJ, Gerhart MJ, Paxton RJ, Black RA, Chang A, Jackson LF.
Ann N Y Acad Sci. 2003 May;995:22-38. (REVIEW)
PMID 12814936
 
Amphiregulin expression in prostatic intraepithelial neoplasia and adenocarcinoma: a study of 93 cases.
Bostwick DG, Qian J, Maihle NJ.
Prostate. 2004 Feb 1;58(2):164-8.
PMID 14716741
 
Clinical relevance of amphiregulin and VEGF in primary breast cancers.
Desruisseau S, Palmari J, Giusti C, Romain S, Martin PM, Berthois Y.
Int J Cancer. 2004 Sep 20;111(5):733-40.
PMID 15252843
 
Prediction of sensitivity of advanced non-small cell lung cancers to gefitinib (Iressa, ZD1839).
Kakiuchi S, Daigo Y, Ishikawa N, Furukawa C, Tsunoda T, Yano S, Nakagawa K, Tsuruo T, Kohno N, Fukuoka M, Sone S, Nakamura Y.
Hum Mol Genet. 2004 Dec 15;13(24):3029-43. Epub 2004 Oct 20.
PMID 15496427
 
Amphiregulin and epidermal growth factor receptor expression in human malignant fibrous histiocytoma of soft tissues.
Yamamoto T, Fujita I, Akisue T, Marui T, Nakatani T, Kawamoto T, Hitora T, Nagira K, Matsumoto K, Kurosaka M.
Anticancer Res. 2004 Mar-Apr;24(2C):1307-10.
PMID 15154665
 
Amphiregulin: an early trigger of liver regeneration in mice.
Berasain C, Garcia-Trevijano ER, Castillo J, Erroba E, Lee DC, Prieto J, Avila MA.
Gastroenterology. 2005 Feb;128(2):424-32.
PMID 15685553
 
Novel role for amphiregulin in protection from liver injury.
Berasain C, Garcia-Trevijano ER, Castillo J, Erroba E, Santamaria M, Lee DC, Prieto J, Avila MA.
J Biol Chem. 2005 May 13;280(19):19012-20. Epub 2005 Mar 7.
PMID 15753092
 
Amphiregulin and epidermal hyperplasia: amphiregulin is required to maintain the psoriatic phenotype of human skin grafts on severe combined immunodeficient mice.
Bhagavathula N, Nerusu KC, Fisher GJ, Liu G, Thakur AB, Gemmell L, Kumar S, Xu ZH, Hinton P, Tsurushita N, Landolfi NF, Voorhees JJ, Varani J.
Am J Pathol. 2005 Apr;166(4):1009-16.
PMID 15793282
 
Amphiregulin causes functional downregulation of adherens junctions in psoriasis.
Chung E, Cook PW, Parkos CA, Park YK, Pittelkow MR, Coffey RJ.
J Invest Dermatol. 2005 Jun;124(6):1134-40.
PMID 15955087
 
Increases of amphiregulin and transforming growth factor-alpha in serum as predictors of poor response to gefitinib among patients with advanced non-small cell lung cancers.
Ishikawa N, Daigo Y, Takano A, Taniwaki M, Kato T, Hayama S, Murakami H, Takeshima Y, Inai K, Nishimura H, Tsuchiya E, Kohno N, Nakamura Y.
Cancer Res. 2005 Oct 15;65(20):9176-84.
PMID 16230376
 
Expression of EGF-family receptors and amphiregulin in multiple myeloma. Amphiregulin is a growth factor for myeloma cells.
Mahtouk K, Hose D, Reme T, De Vos J, Jourdan M, Moreaux J, Fiol G, Raab M, Jourdan E, Grau V, Moos M, Goldschmidt H, Baudard M, Rossi JF, Cremer FW, Klein B.
Oncogene. 2005 May 12;24(21):3512-24.
PMID 15735670
 
Liver regeneration, growth factors, and amphiregulin.
Michalopoulos GK, Khan Z.
Gastroenterology. 2005 Feb;128(2):503-6.
PMID 15685562
 
Bidirectional cross talk between ERalpha and EGFR signalling pathways regulates tamoxifen-resistant growth.
Britton DJ, Hutcheson IR, Knowlden JM, Barrow D, Giles M, McClelland RA, Gee JM, Nicholson RI.
Breast Cancer Res Treat. 2006 Mar;96(2):131-46. Epub 2005 Oct 27.
PMID 16261397
 
Amphiregulin contributes to the transformed phenotype of human hepatocellular carcinoma cells.
Castillo J, Erroba E, Perugorria MJ, Santamaria M, Lee DC, Prieto J, Avila MA, Berasain C.
Cancer Res. 2006 Jun 15;66(12):6129-38.
PMID 16778186
 
Impact of IGF-1R/EGFR cross-talks on hepatoma cell sensitivity to gefitinib.
Desbois-Mouthon C, Cacheux W, Blivet-Van Eggelpoel MJ, Barbu V, Fartoux L, Poupon R, Housset C, Rosmorduc O.
Int J Cancer. 2006 Dec 1;119(11):2557-66.
PMID 16988945
 
Targeting the EGFR pathway for cancer therapy.
Johnston JB, Navaratnam S, Pitz MW, Maniate JM, Wiechec E, Baust H, Gingerich J, Skliris GP, Murphy LC, Los M.
Curr Med Chem. 2006;13(29):3483-92. (REVIEW)
PMID 17168718
 
Control of ErbB signaling through metalloprotease mediated ectodomain shedding of EGF-like factors.
Sanderson MP, Dempsey PJ, Dunbar AJ.
Growth Factors. 2006 Jun;24(2):121-36. (REVIEW)
PMID 16801132
 
Amphiregulin: a new growth factor in hepatocarcinogenesis.
Berasain C, Castillo J, Perugorria MJ, Prieto J, Avila MA.
Cancer Lett. 2007 Aug 28;254(1):30-41. Epub 2007 Feb 26. (REVIEW)
PMID 17321672
 
Expression of epiregulin and amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab.
Khambata-Ford S, Garrett CR, Meropol NJ, Basik M, Harbison CT, Wu S, Wong TW, Huang X, Takimoto CH, Godwin AK, Tan BR, Krishnamurthi SS, Burris HA 3rd, Poplin EA, Hidalgo M, Baselga J, Clark EA, Mauro DJ.
J Clin Oncol. 2007 Aug 1;25(22):3230-7.
PMID 17664471
 
The increasing role of amphiregulin in non-small cell lung cancer.
Busser B, Coll JL, Hurbin A.
Pathol Biol (Paris). 2008 Dec 12. [Epub ahead of print]
PMID 19070973
 
Epidermal growth factor receptor pathway analysis identifies amphiregulin as a key factor for cisplatin resistance of human breast cancer cells.
Eckstein N, Servan K, Girard L, Cai D, von Jonquieres G, Jaehde U, Kassack MU, Gazdar AF, Minna JD, Royer HD.
J Biol Chem. 2008 Jan 11;283(2):739-50. Epub 2007 Oct 17.
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Contributor(s)

Written02-2009Carmen Berasain, Matias A Avila
Division of Hepatology and Gene Therapy, CIMA, University of Navarra, Pamplona, Spain

Citation

This paper should be referenced as such :
Berasain C, Avila MA . AREG (amphiregulin (schwannoma-derived growth factor)). Atlas Genet Cytogenet Oncol Haematol. February 2009 .
URL : http://AtlasGeneticsOncology.org/Genes/AREGID690ch4q13.html

This paper is referenced by INIST as such :
http://documents.irevues.inist.fr/bitstream/2042/44653/1/02-2009-AREGID690ch4q13.pdf   [ Bibliographic record ]

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