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  • Title: Independent regulation of growth and SMAD-mediated transcription by transforming growth factor beta in human melanoma cells.
    Author: Rodeck U, Nishiyama T, Mauviel A.
    Journal: Cancer Res; 1999 Feb 01; 59(3):547-50. PubMed ID: 9973198.
    Abstract:
    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.
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