Defects of TGF-β receptor signaling in mammary cell tumorigenesis

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Abstract
Transforming growth factor β (TGF-β)4 receptor expression and signal transduction in human breast cancer are reviewed as a function of estrogen receptor (ER) expression. ER+ breast cancer cells are generally resistant to the inhibitory effects of TGF-β. The only known exception appears to be MCF-7 early passage cells which are initially sensitive to TGF-β, but gain resistance after long-term passage in tissue culture. A number of studies have shown that loss of sensitivity is due to inadequate TGF-β type II (TGFRII) receptor expression. Stable transfection of TGFRII into ER+ breast cancer cell lines results in the acquisition of TGF-β sensitivity and reversion of malignancy. Although there are exceptions, ER− breast cancer cells usually express TGFRII, but nevertheless show a low level of sensitivity to TGF-β. Thus resistance in these cells implies a postreceptor mechanism. Given the frequency with which loss of TGF-β sensitivity has been associated with loss of TGFRII, the ER− breast cancer cell lines may represent valuable models for identifying postreceptor mechanisms of resistance.