ENHANCED EXPRESSION OF HEREGULIN IN C-ERB B-2 AND C-HA-RAS TRANSFORMED MOUSE AND HUMAN MAMMARY EPITHELIAL-CELLS

Heregulin beta 1 was found to stimulate the anchorage-dependent, serum -free growth of nontransformed human MCF-10A mammary epithelial cells. Unlike epidermal growth factor, transforming growth factor alpha, or amphiregulin, heregulin beta 1 was also able to induce the anchorage-i ndependent growth of MCF-10A cells. In contrast, the anchorage-depende nt, serum-free growth of c-Ha-ras or c-erb B-2 transformed MCF-10A cel ls was unaffected by heregulin beta 1, whereas heregulin beta 1 was ab le to stimulate the anchorage-independent growth of these cells. c-Ha- ras or c-erb B-2 (c-neu) transformed MCF-10A or mouse NOG-8 mammary ep ithelial cells express elevated levels of 2.5, 5.0, 6.5, 6.8, and 8.5 kb heregulin mRNA transcripts and/or synthesize cell-associated 25, 29 , 50, and 115 kDa isoforms of heregulin. Since the MCF-10A cells and t ransformants also express c-erb B-3, these data suggest that endogenou s heregulin might function as an autocrine growth factor for Ha-ras or erb B-2 transformed mammary epithelial cells. (C) 1996 Wiley-Liss, In c.