THE ROLE OF AMPHIREGULIN IN BREAST-CANCER

Amphiregulin (AR) is an epidermal growth factor (EGF)-related peptide that operates exclusively through the EGF receptor and that can bind t o heparin. AR also possesses nuclear localization sequences in the ext ended NH2-terminal region suggesting an additional intracellular site of action. AR mRNA and protein expression have been detected in primar y human mammary epithelial cell strains, nontransformed human mammary epithelial cell lines, several human breast cancer cell lines, and pri mary human breast carcinomas. The frequency and levels of AR protein e xpression are generally higher in invasive breast carcinomas than in d uctal carcinomas in situ or in normal, noninvolved mammary epithelium. In addition, AR can function as an autocrine and/or juxtacrine growth factor in human mammary epithelial cells that have been transformed b y an activated c-Ha-ras proto-oncogene or by overexpression of c-erb B -2. AR expression is also enhanced by mammotrophic hormones such as es trogens and other growth factors such as EGF.