TY - JOUR
T1 - Response of normal and oncogene-transformed human mammary epithelial cells to transforming growth factor β1 (TGF-β1)
T2 - Lack of growth-inhibitory effect on cells expressing the simian virus 40 large-T antigen
AU - Basolo, F.
AU - Fiore, L.
AU - Ciardiello, F.
AU - Calvo, S.
AU - Fontanini, G.
AU - Conaldi, P. G.
AU - Toniolo, A.
PY - 1994
Y1 - 1994
N2 - 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-β1 (TGF-β1) 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-β1 under different test conditions, MEC transformed by c-Ha-ras, c-erbB2, int-2, or SV40-large-T antigen were not inhibited by TGF-β1 in a short-term DNA-synthesis assay. However, in anchorage-dependent conditions TGF-β1 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-β1. Neutralizing antibody to TGF-β 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-β1 on selected surface differentiation molecules was that normal MEC produced increased levels of the human milk fat globule antigen-1. Thus it appears that the response of MEC to TGF-β1 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.
AB - 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-β1 (TGF-β1) 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-β1 under different test conditions, MEC transformed by c-Ha-ras, c-erbB2, int-2, or SV40-large-T antigen were not inhibited by TGF-β1 in a short-term DNA-synthesis assay. However, in anchorage-dependent conditions TGF-β1 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-β1. Neutralizing antibody to TGF-β 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-β1 on selected surface differentiation molecules was that normal MEC produced increased levels of the human milk fat globule antigen-1. Thus it appears that the response of MEC to TGF-β1 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.
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M3 - Article
C2 - 8314352
AN - SCOPUS:0028297389
VL - 56
SP - 736
EP - 742
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 5
ER -