title: Differential effects of fibroblast growth factor and tumor promoters on the initiation and maintenance of adipocyte differentiation.
abstract: Fibroblast growth factor (FGF) has been shown to inhibit the differentiation of myogenic and adipogenic cell lines without inducing a proliferative response. We have previously shown that agents capable of activating protein kinase C (PKC), such as FGF and the phorbol ester tetradecanoyl phorbol-13-acetate (TPA), inhibit the differentiation of the adipogenic cell line TA1, as measured by the rapid loss of adipocyte-specific RNAs. We report here that the treatment of fully differentiated TA1 adipocytes with FGF at 10 ng/ml induces the reversal of adipocyte differentiation, even in cells where PKC activity has been down-regulated by TPA pretreatment. In contrast, TPA or lower concentrations of FGF (1 ng/ml), both effective inducers of c-fos RNA in adipocytes, fail to reverse adipocyte differentiation. The adipocytes, however, will extinguish differentiation-specific functions in response to TPA by the addition of a calcium ionophore. Therefore, we propose that there are two FGF-sensitive pathways in TA1 cells: one responsible for the initiation of differentiation (TPA sensitive) and another required for maintenance of the adipose phenotype (TPA insensitive). These results suggest that activation of two distinct signaling pathways--one PKC and calcium dependent, the other FGF activated but PKC independent--are capable of inhibiting the biochemical events responsible for the maintenance of adipocyte differentiation.
authors.affiliation: Institute of Cancer and Developmental Biology, Syntex Research, Palo Alto, California 94304.
authors.forename: M
authors.initials: M
authors.lastname: Navre
authors.forename: G M
authors.initials: GM
authors.lastname: Ringold
mesh_terms: D000273:Adipose Tissue / Q000166:cytology* / Q000187:drug effects; D000818:Animals; D002273:Carcinogens; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D004261:DNA Replication / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos; D011519:Proto-Oncogenes / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014158:Transcription, Genetic
chemical_list: D002273:Carcinogens; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D015759:Ionomycin; D005346:Fibroblast Growth Factors; D003907:Dexamethasone; D013755:Tetradecanoylphorbol Acetate; D007213:Indomethacin