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Effects of N,N-Dimethylformamide and Retinoic Acid on Transforming Growth Factor-ß Induced Mitogenesis in AKR-2B Mouse Embryo Fibroblasts¹

Bristol-Baylor Laboratory, Department of Pharmacology, Baylor College of Medicine, Houston, Texas 77030

Transforming growth factor-ß (TGF-ß) 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-ß 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-ß blocked the ability of TGF-ß to induce mitogenesis. These agents partially blocked the mitogenic effects of epidermal growth factor and platelet-derived growth factor. DMF blocked TGF-ß induced mitogenesis when added 9 h, but not 24 h, after TGF-ß addition suggesting that DMF affects an early step in the mitogenic cascade induced by TGF-ß. TGF-ß 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-ß inhibited their growth. The addition of DMF under these conditions did not alter the cell's sensitivity to TGF-ß and the cells were still inhibited to the same extent by TGF-ß. Therefore, DMF did not affect the inhibitory action of TGF-ß on AKR-2B fibroblasts but did block the stimulatory effects of TGF-ß.

¹ Supported by Grants BC-492 from the American Cancer Society and CA38100 from the National Cancer Institute, Department of Health and Human Services.

² To whom requests for reprints should be addressed, at Bristol-Baylor Laboratory, Department of Pharmacology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030.

Received 2/ 6/87. Revised 5/ 4/87. Accepted 5/26/87.