Comparison of the effects of transforming growth factor β, N,N-dimethylformamide, and retinoic acid on transformed and nontransformed fibroblasts

Abstract

In order to compare the effects of transforming growth factor (TGFβ) with those of the differentiation promoters N,N-dimethylformamide (DMF) and retinoic acid (RA), the antiproliferative and fibronectin-inducing activities of the three agents were examined. AKR-2B mouse embryo fibroblasts and their chemically transformed counterpart AKR-MCA cells were used as the model system. Growth in monolayer culture of both cell lines was inhibited by TGFβ (EC 50 ~1 ng/ml), DMF (EC 50 ~0.5%), and RA (EC 50 ~1 μ M) in a concentration-dependent manner. Time-dependent elevation in fibronectin expression was also observed with all three agents. The EC 50 for growth inhibition of both cell lines by TGFβ agreed well with that obtained for stimulation of fibronectin synthesis. A 3-h exposure to TGFβ is sufficient to obtain the maximal fibronectin level observed at 48 h in AKR-2B cells but not in AKR-MCA cells. Our results indicate that in this system the effects of TGFβ are similar to those of the chemical differentiation inducers DMF and RA. Furthermore, our data also suggest that the TGFβ signal may be processed differently by nontransformed and transformed fibroblasts.