Mitogenic action of TGF-beta and insulin in L-929 cell line in serum-free medium.

In serum-free medium, TGF-beta, in a wide range of concentrations, stimulated DNA synthesis. A similar effect was achieved with insulin even after relatively short times. When TGF-beta and insulin were present simultaneously, the mitogenic effect was stronger than the effect achieved by either one separately, but without synergism. The PDGF, which is not mitogenic by itself in this cell line, did not increase the response to TGF-beta. In the presence of fetal bovine serum TGF-beta and insulin DNA synthesis was not stimulated. Two of the most important mitogenic growth factors for L-cells present in serum could be insulin and TGF-beta. Adenosine did not modify the mitogenic response to TGF-beta and insulin. However, in the presence of adenosine PDGF stimulated the growth of L-929. The results suggest that TGF-beta does not stimulate the growth of L-929 via an autocrine production of PDGF-related peptides in a serum-free model. TGF-beta blocked the inhibitory response to estradiol at high concentrations, but it did not affect the inhibitory response due to glucocorticoids. Insulin and TGF-beta caused an enhancement of beta-NGF and c-myc RNA expression. This effect appears much earlier with insulin. This difference suggests that mRNA accumulation provoked by TGF-beta is mediated by other factors. Fetal bovine serum had little effect on the expression of those two mRNAs.