Production of and responsiveness to transforming growth factor-beta in normal and oncogene-transformed human mammary epithelial cells.

Transforming growth factors-beta (TGF beta) are a family of closely related, ubiquitously expressed growth factors with the common properties of induction of growth inhibition and expression of differentiation-related markers in epithelial cells. We investigated the role of TGF beta 1 in growth regulation of normal human mammary epithelial cells and in benzo(a)pyrene immortalized sublines further transformed by oncogenes in retroviral vectors. The normal cells were markedly growth inhibited by TGF beta 1, produced TGF beta in a latent form, and expressed TGF beta receptors. In the immortalized cells, both TGF beta-induced growth inhibition and TGF beta receptor binding were reduced. With the single oncogenes v-Ha-ras, v-mos, and SV40 T, growth sensitivity to TGF beta 1 increased, but TGF beta production or TGF beta receptor expression was not altered. Transformation to full malignancy by both SV40 T and v-Ha-ras led to escape from growth inhibition by TGF beta under anchorage-independent, but not anchorage-dependent, conditions without affecting TGF beta production or receptor characteristics. Thus, modulation of TGF beta growth responsiveness in these normal and oncogene transformed human mammary epithelial cells apparently occurs at a level distal to TGF beta receptor binding and is not solely correlated to expression of transforming oncogenes. Further, modulation of TGF beta production is not an indicator of malignant transformation in this system.