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Int J Cancer. 1994 Mar 1;56(5):736-42.

Response of normal and oncogene-transformed human mammary epithelial cells to transforming growth factor beta 1 (TGF-beta 1): lack of growth-inhibitory effect on cells expressing the simian virus 40 large-T antigen.

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Institute of Pathological Anatomy, University of Pisa, Italy.


The relationship between the expression of selected oncogenes having different modes of action and the loss of the capacity to respond in vitro to transforming growth factor-beta I (TGF-beta I) was analyzed in human mammary epithelial cells (MEC). Primary MEC cultures from healthy donors and the spontaneously immortalized MCF-10A cell line were used as normal controls. Various assays (employing both complete and chemically defined media) were used: short-term DNA synthesis, long-term cell proliferation under anchorage-dependent and -independent conditions, expression of surface-differentiation molecules. Whereas primary MEC and the MCF-10A cell line were fully responsive to the growth-inhibitory activity of TGF-beta I under different test conditions, MEC transformed by c-Ha-ras, c-erbB2, int-2, or SV40-large-T antigen were not inhibited by TGF-beta I in a short-term DNA-synthesis assay. However, in anchorage-dependent conditions TGF-beta I inhibited the proliferation of all lines investigated, with the exception of SV40-T-antigen-transformed MEC. The colony-formation assay in soft agar revealed that all lines, but not those expressing the int-2 or the SV40-T-antigen genes, were inhibited by TGF-beta I. Neutralizing antibody to TGF-beta had no significant effects on oncogene-transformed lines, suggesting that the endogenous production of an active form of this growth factor is not a major determinant in MEC transformation by the oncogenes investigated. The only observed effect of TGF-beta I on selected surface-differentiation molecules was that normal MEC produced increased levels of the human milk fat globule antigen-I. Thus it appears that the response of MEC to TGF-beta I is consistently attenuated by the insertion of a variety of oncogenes and that it is abolished only by the expression of the SV40-large-T antigen. Whereas no single in vitro assay was capable of accurately reflecting the actual responsiveness of different lines, the growth-curve assay in anchorage-dependent conditions was the best single predictive test.

[Indexed for MEDLINE]

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