Effects of N,N-dimethylformamide and retinoic acid on transforming growth factor-beta induced mitogenesis in AKR-2B mouse embryo fibroblasts.
Transforming growth factor-beta (TGF-beta) is a bifunctional reagent which can exert both stimulatory and inhibitory effects upon the same target cell. Treatment of growth arrested AKR-2B mouse embryo fibroblasts with TGF-beta has been shown to stimulate mitogenesis by an indirect mechanism. Addition of the differentiation agents N,N-dimethylformamide (DMF) or retinoic acid simultaneously with TGF-beta blocked the ability of TGF-beta to induce mitogenesis. These agents partially blocked the mitogenic effects of epidermal growth factor and platelet-derived growth factor. DMF blocked TGF-beta induced mitogenesis when added 9 h, but not 24 h, after TGF-beta addition suggesting that DMF affects an early step in the mitogenic cascade induced by TGF-beta. TGF-beta will induce anchorage independent growth in AKR-2B fibroblasts and this was also inhibited by DMF. When AKR-2B cells were grown in monolayer culture, TGF-beta inhibited their growth. The addition of DMF under these conditions did not alter the cell's sensitivity to TGF-beta and the cells were still inhibited to the same extent by TGF-beta. Therefore, DMF did not affect the inhibitory action of TGF-beta on AKR-2B fibroblasts but did block the stimulatory effects of TGF-beta.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004126:Dimethylformamide / Q000494:pharmacology*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology; D051379:Mice; D008938:Mitosis / Q000187:drug effects*; D010455:Peptides / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D015291:Transforming Growth Factors; D014212:Tretinoin / Q000494:pharmacology*
D010455:Peptides; D010982:Platelet-Derived Growth Factor; D014212:Tretinoin; D004815:Epidermal Growth Factor; D015291:Transforming Growth Factors; D004126:Dimethylformamide; D013936:Thymidine