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Heparin inhibition of autonomous growth implicates amphiregulin as an autocrine growth factor for normal human mammary epithelial cells
Author(s) -
Li Shiwei,
Plowman Gregory D.,
Buckley Sharon D.,
Shipley Gary D.
Publication year - 1992
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041530114
Subject(s) - amphiregulin , autocrine signalling , biology , epidermal growth factor , growth factor , cell culture , transforming growth factor , tgf alpha , heparin binding egf like growth factor , microbiology and biotechnology , receptor , biochemistry , genetics
Normal human mammary epithelial cells (HMECs) proliferate in a serum‐free defined growth medium in the absence of epidermal growth factor (Li and Shipley, 1991). Amphiregulin (AR) is a heparin‐regulated, EGF‐like growth factor. Our observation that one strain of HMECs produce AR mRNA (Cook et al., 1991a) stimulated us to determine whether AR expression was a common phenomenon in HMECs and whether AR could act as an autocrin growth factor to support the EGF‐independent growth of these cells. In this study, we detected high levels of AR expression in four separate HMEC strains while one immortal mammary cell line (HBL‐100) and six mammary tumor‐derived cell lines had low to undetectable levels of AR. The EGF‐indendent growth of HMECs was blocked by the addition of heparin or a monoclonal anti‐RGF receptors antibody to the culture medium, implication AR as an autocrine growth mediator. This hypothesis is further supported by the fact that medium conditioned by HMECs contains secreted AR protein. A mammary tumor‐derived cell line, Hs578T, which proliferates in an EGF‐independent manner, does not express detectable levels of AR and is not growth inhibited by heparin. Examination of the same cell types for expression of transforming growth factor type‐alpha (TGF‐α) mRNA revealed coordinate expression of AR and TGF‐α in these cells. These data suggest that both AR and TGF‐α mRNA are produced in much greater abundance by normal HMECs than in tumor‐derived cells in culture, and that AR is an important autostimulatory factor for the growth of normal HMECs. © 1992 Wiley‐Liss, Inc.