Altered responsiveness of rat liver epithelial cells to transforming growth factor β1 following their transformation with v-raf

Abstract The effects of transforming growth factor β (type 1) (TGF-β 1 ) on DNA synthesis, cell proliferation, and protein synthesis were examined in a series of v- raf -transformed rat liver epithelial (RLE) cells, which exhibit a range of transformed phenotypes. All of the transformed cells were relatively resistant to the growth-inhibitory effects of TGF-β 1 , compared to normal RLE cells and control cells infected with a helper virus. The more tumorigenic cell lines had very few surface receptors for TGF-β 1 and showed no increase in the secretion of a number of specific proteins, including fibronectin, following TGF-β 1 treatment. In contrast, the more normal-looking, less tumorigenic v- raf -transformed cells bound similar amounts of TGF-β 1 as normal RLE and control cells and showed a similar pattern of TGF-β 1 -stimulated protein secretion. These findings suggest that the effects of TGF-β 1 on cell proliferation and on the expression of certain secreted proteins are mediated through different mechanisms. Following transformation of RLE cells with v- raf , the signalling pathways controlling TGF-β 1 growth inhibition are perturbed, while those involved in regulating the synthesis of certain proteins may remain intact. Thus, the escape from the various distinct biological effects of TGF-β 1 may be an important stage in the progression of neoplastic transformation of RLE cells in vitro .