Amphiregulin

Amphiregulin
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2RNL​
Identifiers
Symbols	AREG ; AR; AREGB; CRDGF; SDGF
External IDs	OMIM: 104640 MGI: 88068 HomoloGene: 1252 ChEMBL: 3731 GeneCards: AREG Gene
Gene ontology Molecular function • cytokine activity • epidermal growth factor receptor binding • protein binding • growth factor activity Cellular component • extracellular space • nucleus • cytoplasm • cell surface • integral component of membrane Biological process • epidermal growth factor receptor signaling pathway • G-protein coupled receptor signaling pathway • cell-cell signaling • cell proliferation • positive regulation of cell proliferation • glial cell proliferation • neuron projection development • response to estradiol • positive regulation of phosphorylation • response to hydrogen peroxide • response to peptide hormone • negative regulation of osteoblast differentiation • positive regulation of DNA replication • response to glucocorticoid • response to cAMP • dichotomous subdivision of terminal units involved in mammary gland duct morphogenesis • mammary gland branching involved in thelarche • mammary gland alveolus development • epithelial cell proliferation involved in mammary gland duct elongation Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	374	11839
Ensembl	ENSG00000109321	ENSMUSG00000029378
UniProt	P15514	P31955
RefSeq (mRNA)	NM_001657	NM_009704
RefSeq (protein)	NP_001648	NP_033834
Location (UCSC)	Chr 4: 74.45 – 74.46 Mb	Chr 5: 91.14 – 91.15 Mb
PubMed search

Amphiregulin, also known as AREG, is a protein that in humans is encoded by the AREG gene.^[1][2][3]

Function

The protein encoded by this gene is a member of the epidermal growth factor (EGF) family.^[1]

It is an autocrine growth factor as well as a mitogen for astrocytes, Schwann cells, fibroblasts. It is related to epidermal growth factor (EGF) and transforming growth factor alpha (TGF-alpha). This protein interacts with the Epidermal growth factor receptor (EGFR) to promote the growth of normal epithelial cells.

Biological role

Estradiol and progesterone mostly induce amphiregulin expression to mediate ductal development of the mammary glands.^{[4][5][6][7][8]} Amphiregulin has been found to be essential for mammary ductal development, as evidenced by absence of ductal growth in amphiregulin knockout mice.^[7] This is similar to the phenotypes of EGFR and ERα knockout mice, which also show absence of ductal growth.^[7]

Clinical signficance

Mutations in this encoded protein are associated with a psoriasis-like skin phenotype.^[1]

References

1. "Entrez Gene: AREG amphiregulin (schwannoma-derived growth factor)".
2. Shoyab M, Plowman GD, McDonald VL, Bradley JG, Todaro GJ (February 1989). "Structure and function of human amphiregulin: a member of the epidermal growth factor family". Science 243 (4894 Pt 1): 1074–6. doi:10.1126/science.2466334. PMID 2466334.
3. Plowman GD, Green JM, McDonald VL, Neubauer MG, Disteche CM, Todaro GJ, Shoyab M (May 1990). "The amphiregulin gene encodes a novel epidermal growth factor-related protein with tumor-inhibitory activity". Mol. Cell. Biol. 10 (5): 1969–81. PMC 360543. PMID 2325643.
4. Aupperlee MD, Leipprandt JR, Bennett JM, Schwartz RC, Haslam SZ (2013). "Amphiregulin mediates progesterone-induced mammary ductal development during puberty". Breast Cancer Res. 15 (3): R44. doi:10.1186/bcr3431. PMC 3738150. PMID 23705924.
5. LaMarca HL, Rosen JM (2007). "Estrogen regulation of mammary gland development and breast cancer: amphiregulin takes center stage". Breast Cancer Res. 9 (4): 304. doi:10.1186/bcr1740. PMC 2206713. PMID 17659070.
6. Kariagina A, Xie J, Leipprandt JR, Haslam SZ (2010). "Amphiregulin mediates estrogen, progesterone, and EGFR signaling in the normal rat mammary gland and in hormone-dependent rat mammary cancers". Horm Cancer 1 (5): 229–44. doi:10.1007/s12672-010-0048-0. PMC 3000471. PMID 21258428.
7. McBryan J, Howlin J, Napoletano S, Martin F (2008). "Amphiregulin: role in mammary gland development and breast cancer". J Mammary Gland Biol Neoplasia 13 (2): 159–69. doi:10.1007/s10911-008-9075-7. PMID 18398673.
8. Sternlicht MD, Sunnarborg SW (2008). "The ADAM17-amphiregulin-EGFR axis in mammary development and cancer". J Mammary Gland Biol Neoplasia 13 (2): 181–94. doi:10.1007/s10911-008-9084-6. PMC 2723838. PMID 18470483.

Further reading

• Culouscou JM, Remacle-Bonnet M, Carlton GW; et al. (1993). "Colorectum cell-derived growth factor (CRDGF) is homologous to amphiregulin, a member of the epidermal growth factor family". Growth Factors 7 (3): 195–205. doi:10.3109/08977199209046924. PMID 1333777.
• Cook PW, Mattox PA, Keeble WW; et al. (1991). "A heparin sulfate-regulated human keratinocyte autocrine factor is similar or identical to amphiregulin". Mol. Cell. Biol. 11 (5): 2547–57. PMC 360024. PMID 2017164.
• Kimura H, Fischer WH, Schubert D (1990). "Structure, expression and function of a schwannoma-derived growth factor". Nature 348 (6298): 257–60. doi:10.1038/348257a0. PMID 2234093.
• Plowman GD, Green JM, McDonald VL; et al. (1990). "The amphiregulin gene encodes a novel epidermal growth factor-related protein with tumor-inhibitory activity". Mol. Cell. Biol. 10 (5): 1969–81. PMC 360543. PMID 2325643.
• Shoyab M, Plowman GD, McDonald VL; et al. (1989). "Structure and function of human amphiregulin: a member of the epidermal growth factor family". Science 243 (4894 Pt 1): 1074–6. doi:10.1126/science.2466334. PMID 2466334.
• Shoyab M, McDonald VL, Bradley JG, Todaro GJ (1988). "Amphiregulin: a bifunctional growth-modulating glycoprotein produced by the phorbol 12-myristate 13-acetate-treated human breast adenocarcinoma cell line MCF-7". Proc. Natl. Acad. Sci. U.S.A. 85 (17): 6528–32. doi:10.1073/pnas.85.17.6528. PMC 282006. PMID 3413110.
• Chen CS, Bejcek BE, Kersey JH (1995). "A mapping study of 13 genes on human chromosome bands 4q11→q25". Cytogenet. Cell Genet. 69 (3–4): 260–5. doi:10.1159/000133976. PMID 7698025.
• Cook PW, Piepkorn M, Clegg CH; et al. (1997). "Transgenic expression of the human amphiregulin gene induces a psoriasis-like phenotype". J. Clin. Invest. 100 (9): 2286–94. doi:10.1172/JCI119766. PMC 508424. PMID 9410906.
• Wong L, Deb TB, Thompson SA; et al. (1999). "A differential requirement for the COOH-terminal region of the epidermal growth factor (EGF) receptor in amphiregulin and EGF mitogenic signaling". J. Biol. Chem. 274 (13): 8900–9. doi:10.1074/jbc.274.13.8900. PMID 10085134.
• Reddy KB, Krueger JS, Kondapaka SB, Diglio CA (1999). "Mitogen-activated protein kinase (MAPK) regulates the expression of progelatinase B (MMP-9) in breast epithelial cells". Int. J. Cancer 82 (2): 268–73. doi:10.1002/(SICI)1097-0215(19990719)82:2<268::AID-IJC18>3.0.CO;2-4. PMID 10389762.
• Fernandes AM, Hamburger AW, Gerwin BI (1999). "Production of epidermal growth factor related ligands in tumorigenic and benign human lung epithelial cells". Cancer Lett. 142 (1): 55–63. doi:10.1016/S0304-3835(99)00166-4. PMID 10424781.
• Lee SB, Huang K, Palmer R; et al. (1999). "The Wilms tumor suppressor WT1 encodes a transcriptional activator of amphiregulin". Cell 98 (5): 663–73. doi:10.1016/S0092-8674(00)80053-7. PMID 10490105.
• Tokumaru S, Higashiyama S, Endo T; et al. (2000). "Ectodomain Shedding of Epidermal Growth Factor Receptor Ligands Is Required for Keratinocyte Migration in Cutaneous Wound Healing". J. Cell Biol. 151 (2): 209–20. doi:10.1083/jcb.151.2.209. PMC 2192647. PMID 11038170.
• Ebert MP, Hernberg S, Fei G; et al. (2001). "Induction and expression of cyclin D3 in human pancreatic cancer". J. Cancer Res. Clin. Oncol. 127 (7): 449–54. doi:10.1007/s004320100235. PMID 11469683.
• Berquin IM, Dziubinski ML, Nolan GP, Ethier SP (2001). "A functional screen for genes inducing epidermal growth factor autonomy of human mammary epithelial cells confirms the role of amphiregulin". Oncogene 20 (30): 4019–28. doi:10.1038/sj.onc.1204537. PMID 11494130.
• Thøgersen VB, Sørensen BS, Poulsen SS; et al. (2001). "A subclass of HER1 ligands are prognostic markers for survival in bladder cancer patients". Cancer Res. 61 (16): 6227–33. PMID 11507076.
• Wolfgang CD, Essand M, Lee B, Pastan I (2001). "T-cell receptor gamma chain alternate reading frame protein (TARP) expression in prostate cancer cells leads to an increased growth rate and induction of caveolins and amphiregulin". Cancer Res. 61 (22): 8122–6. PMID 11719440.
• Schiemann U, Konturek J, Assert R; et al. (2002). "mRNA expression of EGF receptor ligands in atrophic gastritis before and after Helicobacter pylori eradication". Med. Sci. Monit. 8 (2): CR53–8. PMID 11859273.
• Tørring N, Møller-Ernst Jensen K, Lund L; et al. (2002). "Possible autocrine loop of the epidermal growth factor system in patients with benign prostatic hyperplasia treated with finasteride: a placebo-controlled randomized study". BJU Int. 89 (6): 583–90. doi:10.1046/j.1464-410X.2002.02665.x. PMID 11942969.
• Hurbin A, Dubrez L, Coll JL, Favrot MC (2003). "Inhibition of apoptosis by amphiregulin via an insulin-like growth factor-1 receptor-dependent pathway in non-small cell lung cancer cell lines". J. Biol. Chem. 277 (51): 49127–33. doi:10.1074/jbc.M207584200. PMID 12356750.