Production of and Responsiveness to Transforming Growth Factor- β in Normal and Oncogene-transformed Human Mammary Epithelial Cells

Transforming growth factors-β (TGFβ) 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 TGFβ₁ 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 TGFβ₁, produced TGFβ in a latent form, and expressed TGFβ receptors. In the immortalized cells, both TGFβ-induced growth inhibition and TGFβ receptor binding were reduced. With the single oncogenes v-Ha-ras, v-mos, and SV40 T, growth sensitivity to TGFβ₁ increased, but TGFβ production or TGFβ receptor expression was not altered. Transformation to full malignancy by both SV40 T and v-Ha-ras led to escape from growth inhibition by TGFβ under anchorage-independent, but not anchorage-dependent, conditions without affecting TGFβ production or receptor characteristics. Thus, modulation of TGFβ growth responsiveness in these normal and oncogene transformed human mammary epithelial cells apparently occurs at a level distal to TGFβ receptor binding and is not solely correlated to expression of transforming oncogenes. Further, modulation of TGFβ production is not an indicator of malignant transformation in this system.