Amphiregulin: role in mammary gland development and breast cancer.
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.
McBryan
Jean
J
School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.
Howlin
Jillian
J
Napoletano
Silvia
S
Martin
Finian
F
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
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