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Amphiregulin

AREG
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesAREG, AR, AREGB, CRDGF, SDGF, amphiregulin
External IDsOMIM: 104640 MGI: 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]
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001657

NM_009704

RefSeq (protein)

NP_001648

NP_033834

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

Amphiregulin, also known as AREG, is a protein syntetized as a transmembrane glykoprotein with 252 aminoacids and it is encoded by the AREG gene.[5][6][7] in human[8].

Function

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

It is a critical autocrine growth factor as well as a mitogen for astrocytes, Schwann cells, and fibroblasts. It is ligand for epidermal growth factor (EGF) and it is related to 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

AREG is a critical factor in estrogen action and ductal development of the mammary glands.[9][10][11][12][13] Amphiregulin has been found to be essential for mammary ductal development, as evidenced by absence of ductal growth in amphiregulin knockout mice.[12] This is similar to the phenotypes of EGFR and ERα knockout mice, which also show absence of ductal growth.[12] Amphiregulin is expressed in many parts of body such as ovaries, placenta, pancreas, breasts, lungs and spleen. Expression of amphiregulin can be induced by TGF-α, TNF-α, interleukin 1, and prostaglandins.[14][15]

Clinical significance

Psoriasis

Mutations in this encoded protein are associated with a psoriasis-like skin phenotype[16][5]. Higher circulating levels of amphiregulin are associated with AGVHD progression.[17] [18][19]

Cancer

Overexpression of amphiregulin is connected with cancer of the breast, prostate, colon, pancreas, lung, spleen, and bladder.[20][21][22]

Rheumatoid arthritis

It seems that expression of AREG is connected with proliferation of fibroblasts and production of proinflammatory cytokines interleukin 8 and vascular endothelial growth factor (VEGF).[23]

Inflammation

Amphiregulin is part of cellular response type 2[24]. It was found that the cell source of amphiregulin is innate lymphoid cells 2 (ILC2) which are dependent on interleukin 33. ILC2 expressed amphiregulin after tissue damage of the intestines and activation by IL-33. Moreover, endogenous AREG with IL-33 decreased the intestinal inflammation in mice with normal count of T-lymphocytes and in deficient mice[25].

References

  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:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  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): 1074–6. 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): 1969–81. doi:10.1128/MCB.10.5.1969. PMC 360543. PMID 2325643.
  8. ^ "AREG (amphiregulin (schwannoma-derived growth factor))". atlasgeneticsoncology.org. Retrieved 2019-08-27.
  9. ^ Aupperlee MD, Leipprandt JR, Bennett JM, Schwartz RC, Haslam SZ (May 2013). "Amphiregulin mediates progesterone-induced mammary ductal development during puberty". Breast Cancer Research. 15 (3): R44. doi:10.1186/bcr3431. PMC 3738150. PMID 23705924.
  10. ^ 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.
  11. ^ Kariagina A, Xie J, Leipprandt JR, Haslam SZ (October 2010). "Amphiregulin mediates estrogen, progesterone, and EGFR signaling in the normal rat mammary gland and in hormone-dependent rat mammary cancers". Hormones & Cancer. 1 (5): 229–44. doi:10.1007/s12672-010-0048-0. PMC 3000471. PMID 21258428.
  12. ^ a b c McBryan J, Howlin J, Napoletano S, Martin F (June 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.
  13. ^ Sternlicht MD, Sunnarborg SW (June 2008). "The ADAM17-amphiregulin-EGFR axis in mammary development and cancer". Journal of Mammary Gland Biology and Neoplasia. 13 (2): 181–94. doi:10.1007/s10911-008-9084-6. PMC 2723838. PMID 18470483.
  14. ^ "AREG (amphiregulin (schwannoma-derived growth factor))". atlasgeneticsoncology.org. Retrieved 2019-08-27.
  15. ^ Busser B, Sancey L, Brambilla E, Coll JL, Hurbin A (December 2011). "The multiple roles of amphiregulin in human cancer". Biochimica et Biophysica Acta. 1816 (2): 119–31. doi:10.1016/j.bbcan.2011.05.003. PMID 21658434.
  16. ^ Bhagavathula N, Nerusu KC, Fisher GJ, Liu G, Thakur AB, Gemmell L, et al. (April 2005). "Amphiregulin and epidermal hyperplasia: amphiregulin is required to maintain the psoriatic phenotype of human skin grafts on severe combined immunodeficient mice". The American Journal of Pathology. 166 (4): 1009–16. doi:10.1016/S0002-9440(10)62322-X. PMC 1780140. PMID 15793282.
  17. ^ Bhagavathula N, Nerusu KC, Fisher GJ, Liu G, Thakur AB, Gemmell L, et al. (April 2005). "Amphiregulin and epidermal hyperplasia: amphiregulin is required to maintain the psoriatic phenotype of human skin grafts on severe combined immunodeficient mice". The American Journal of Pathology. 166 (4): 1009–16. doi:10.1016/S0002-9440(10)62322-X. PMC 1780140. PMID 15793282.
  18. ^ Holtan SG, DeFor TE, Panoskaltsis-Mortari A, Khera N, Levine JE, Flowers ME, et al. (August 2018). "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. PMC 6093743. PMID 30087106.
  19. ^ Piepkorn M (April 1996). "Overexpression of amphiregulin, a major autocrine growth factor for cultured human keratinocytes, in hyperproliferative skin diseases". The American Journal of Dermatopathology. 18 (2): 165–71. doi:10.1097/00000372-199604000-00010. PMID 8739992.
  20. ^ Busser B, Sancey L, Brambilla E, Coll JL, Hurbin A (December 2011). "The multiple roles of amphiregulin in human cancer". Biochimica et Biophysica Acta. 1816 (2): 119–31. doi:10.1016/j.bbcan.2011.05.003. PMID 21658434.
  21. ^ "AREG (amphiregulin (schwannoma-derived growth factor))". atlasgeneticsoncology.org. Retrieved 2019-08-27.
  22. ^ McBryan J, Howlin J, Napoletano S, Martin F (June 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.
  23. ^ Yamane S, Ishida S, Hanamoto Y, Kumagai K, Masuda R, Tanaka K, et al. (April 2008). "Proinflammatory role of amphiregulin, an epidermal growth factor family member whose expression is augmented in rheumatoid arthritis patients". Journal of Inflammation. 5: 5. doi:10.1186/1476-9255-5-5. PMC 2396620. PMID 18439312.
  24. ^ Zaiss DM, Yang L, Shah PR, Kobie JJ, Urban JF, Mosmann TR (December 2006). "Amphiregulin, a TH2 cytokine enhancing resistance to nematodes". Science. 314 (5806): 1746. doi:10.1126/science.1133715. PMID 17170297.
  25. ^ Monticelli LA, Osborne LC, Noti M, Tran SV, Zaiss DM, Artis D (August 2015). "IL-33 promotes an innate immune pathway of intestinal tissue protection dependent on amphiregulin-EGFR interactions". Proceedings of the National Academy of Sciences of the United States of America. 112 (34): 10762–7. doi:10.1073/pnas.1509070112. PMC 4553775. PMID 26243875.

Further reading

External links