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Available structures
PDBOrtholog search: PDBe RCSB
AliasesAREG, AR, AREGB, CRDGF, SDGF, amphiregulin
External IDsMGI: 88068 HomoloGene: 1252 GeneCards: AREG
Gene location (Human)
Chromosome 4 (human)
Chr.Chromosome 4 (human)[1]
Chromosome 4 (human)
Genomic location for AREG
Genomic location for AREG
Band4q13.3Start74,445,136 bp[1]
End74,455,005 bp[1]
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC)Chr 4: 74.45 – 74.46 MbChr 5: 91.14 – 91.15 Mb
PubMed search[3][4]
View/Edit HumanView/Edit Mouse

Amphiregulin, also known as AREG, is a protein that in humans is encoded by the AREG gene.[5][6][7]


The protein encoded by this gene is a member of the epidermal growth factor (EGF) family.[5]

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[edit]

Estradiol and progesterone mostly induce amphiregulin expression to mediate ductal development of the mammary glands.[8][9][10][11][12] Amphiregulin has been found to be essential for mammary ductal development, as evidenced by absence of ductal growth in amphiregulin knockout mice.[11] This is similar to the phenotypes of EGFR and ERα knockout mice, which also show absence of ductal growth.[11]

Clinical significance[edit]

Mutations in this encoded protein are associated with a psoriasis-like skin phenotype.[5] Higher circulating levels of amphiregulin are associated with AGVHD progression. [13]


  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000109321 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000029378 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:".
  4. ^ "Mouse PubMed Reference:".
  5. ^ a b c "Entrez Gene: AREG amphiregulin (schwannoma-derived growth factor)".
  6. ^ 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): 1074–1076. doi:10.1126/science.2466334. PMID 2466334.
  7. ^ 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". Molecular and Cellular Biology. 10 (5): 1969–1981. doi:10.1128/MCB.10.5.1969. PMC 360543. PMID 2325643.
  8. ^ Aupperlee MD, Leipprandt JR, Bennett JM, Schwartz RC, Haslam SZ (2013). "Amphiregulin mediates progesterone-induced mammary ductal development during puberty". Breast Cancer Research. 15 (3): R44. doi:10.1186/bcr3431. PMC 3738150. PMID 23705924.
  9. ^ LaMarca HL, Rosen JM (2007). "Estrogen regulation of mammary gland development and breast cancer: amphiregulin takes center stage". Breast Cancer Research. 9 (4): 304. doi:10.1186/bcr1740. PMC 2206713. PMID 17659070.
  10. ^ 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". Hormones and Cancer. 1 (5): 229–244. doi:10.1007/s12672-010-0048-0. PMC 3000471. PMID 21258428.
  11. ^ a b c McBryan J, Howlin J, Napoletano S, Martin F (2008). "Amphiregulin: role in mammary gland development and breast cancer". Journal of Mammary Gland Biology and Neoplasia. 13 (2): 159–69. doi:10.1007/s10911-008-9075-7. PMID 18398673.
  12. ^ Sternlicht MD, Sunnarborg SW (2008). "The ADAM17-amphiregulin-EGFR axis in mammary development and cancer". Journal of Mammary Gland Biology and Neoplasia. 13 (2): 181–194. doi:10.1007/s10911-008-9084-6. PMC 2723838. PMID 18470483.
  13. ^ MacMillan, Margaret L.; Weisdorf, Daniel J.; Blazar, Bruce R.; Alousi, Amin; Ho, Vincent; Bolaños-Meade, Javier; Wu, Juan; Howard, Alan; Pidala, Joseph (2018-08-14). "Amphiregulin modifies the Minnesota Acute Graft-versus-Host Disease Risk Score: results from BMT CTN 0302/0802". Blood Advances. 2 (15): 1882–1888. doi:10.1182/bloodadvances.2018017343. ISSN 2473-9529. PMC 6093743. PMID 30087106.

External links[edit]

Further reading[edit]