Independent regulation of growth and SMAD-mediated transcription by transforming growth factor beta in human melanoma cells.

Increased production of transforming growth factor beta (TGF-beta) coupled with resistance to the growth-inhibitory effects of TGF-beta is characteristic of several types of neoplasia including human melanoma. In select epithelial malignancies, lack of TGF-beta-induced growth inhibition is associated with disruptions of TGF-beta-dependent SMAD signaling and transcription. In contrast, the results of the present study indicate intact SMAD-dependent transcription in human melanoma cells, regardless of their proliferative response to exogenous TGF-beta. Furthermore, in some melanoma cell lines constitutive SMAD-dependent transcription was observed, which was due in part to endogenous TGF-beta. These results establish that resistance of melanoma cells to TGF-beta-induced growth inhibition occurs independently of intact TGF-beta receptor/SMAD-mediated transcriptional regulation. They also suggest that melanoma-derived TGF-beta may exert autocrine effects on SMAD-sensitive target genes.