title: Amphiregulin: role in mammary gland development and breast cancer.
abstract: Extensive epithelial cell proliferation underlies the ductal morphogenesis of puberty that generates the mammary tree that will eventually fill the fat pad. This estrogen-dependent process is believed to be essentially dependent on locally produced growth factors that act in a paracrine fashion. EGF-like growth factor ligands, acting through EGF receptors are some of the principal promoters of pubertal ductal morphogenesis. Amphiregulin is the most abundant EGF-like growth factor in the pubertal mammary gland. Its gene is transcriptionally regulated by ERalpha, and recent evidence identifies it as a key mediator of the estrogen-driven epithelial cell proliferation of puberty: The pubertal deficiency in mammary gland ductal morphogenesis in ERalpha, amphiregulin, and EGFR knockout mice phenocopy each other. As a prognostic indicator in human breast cancer, amphiregulin indicates an outcome identical to that predicted by ERalpha presence. Despite this, a range of studies both on preneoplastic human breast tissue and on cell culture based models of breast cancer, suggest a possibly significant role for amphiregulin in driving human breast cancer progression. Here we summarise our current understanding of amphiregulin's contribution to mammary gland development and breast cancer progression.
authors.affiliation: School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Jean
authors.initials: J
authors.lastname: McBryan
authors.forename: Jillian
authors.initials: J
authors.lastname: Howlin
authors.forename: Silvia
authors.initials: S
authors.lastname: Napoletano
authors.forename: Finian
authors.initials: F
authors.lastname: Martin
mesh_terms: D066258:Amphiregulin; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D004195:Disease Models, Animal; D066255:EGF Family of Proteins; D004967:Estrogens / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008321:Mammary Glands, Animal / Q000254:growth & development* / Q000378:metabolism; D042361:Mammary Glands, Human / Q000254:growth & development* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009024:Morphogenesis; D011627:Puberty
chemical_list: C587848:AREG protein, human; D066258:Amphiregulin; C587849:Areg protein, mouse; D014408:Biomarkers, Tumor; D066255:EGF Family of Proteins; D004967:Estrogens; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins