Available structures
PDBOrtholog search: PDBe RCSB
Aliases AREG, AR, AREGB, CRDGF, SDGF, amphiregulin
External IDs MGI: 88068 HomoloGene: 1252 GeneCards: AREG
Species Human Mouse









RefSeq (mRNA)



RefSeq (protein)



Location (UCSC) Chr 4: 74.45 – 74.46 Mb Chr 5: 91.14 – 91.15 Mb
PubMed search [1] [2]
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Amphiregulin, also known as AREG, is a protein that in humans is encoded by the AREG gene.[3][4][5]


The protein encoded by this gene is a member of the epidermal growth factor (EGF) family.[3]

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.[6][7][8][9][10] Amphiregulin has been found to be essential for mammary ductal development, as evidenced by absence of ductal growth in amphiregulin knockout mice.[9] This is similar to the phenotypes of EGFR and ERα knockout mice, which also show absence of ductal growth.[9]

Clinical signficance

Mutations in this encoded protein are associated with a psoriasis-like skin phenotype.[3]


  1. "Human PubMed Reference:".
  2. "Mouse PubMed Reference:".
  3. 1 2 3 "Entrez Gene: AREG amphiregulin (schwannoma-derived growth factor)".
  4. 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.
  5. 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 360543Freely accessible. PMID 2325643.
  6. 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 3738150Freely accessible. PMID 23705924.
  7. 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 2206713Freely accessible. PMID 17659070.
  8. 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 3000471Freely accessible. PMID 21258428.
  9. 1 2 3 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.
  10. 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 2723838Freely accessible. PMID 18470483.

Further reading

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