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.
Rodeck
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U
Department of Dermatology and Cutaneous Biology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Nishiyama
T
T
Mauviel
A
A
D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008544:Melanocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D015534:Trans-Activators / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology / Q000502:physiology*; D014407:Tumor Cells, Cultured