Enhanced expression of heregulin in c-erb B-2 and c-Ha-ras transformed mouse and human mammary epithelial cells

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Abstract
Heregulin β1 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 α, or amphiregulin, heregulin β1 was also able to induce the anchorage‐independent growth of MCF‐10A cells. In contrast, the anchorage‐dependent, serum‐free growth of c‐Ha‐ras or c‐erb B‐2 transformed MCF‐10A cells was unaffected by heregulin β1, whereas heregulin β1 was able 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 epithelial 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 transformants also express c‐erb B‐3, these data suggest that endogenous heregulin might function as an autocrine growth factor for Ha‐ras or erb B‐2 transformed mammary epithelial cells. © 1996 Wiley‐Liss, Inc. 1 This article is a US Government work and, as such, is in the public domain in the United States of America.