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, sti mulated 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 achi eved by either one separately, but without synergism. The PDGF, which is not mitogenic by itself in this cell line, did not increase the res ponse to TGF-beta. In the presence of fetal bovine serum TGF-beta and insulin DNA synthesis was not stimulated. Two of the most important mi togenic growth factors for L-cells present in serum could be insulin a nd TGF-beta. Adenosine did not modify the mitogenic response to TGF-be ta and insulin. However, in the presence of adenosine PDGF stimulated the growth of L-929. The results suggest that TGF-beta does not stimul ate the growth of L-929 via an autocrine production of PDGF-related pe ptides in a serum-free model. TGF-beta blocked the inhibitory response to estradiol at high concentrations, but it did not affect the inhibi tory response due to glucocorticoids. Insulin and TGF-beta caused an e nhancement of beta-NGF and c-myc RNA expression. This effect appears m uch earlier with insulin. This difference suggests that mRNA accumulat ion provoked by TGF-beta is mediated by other factors. Fetal bovine se rum had little effect on the expression of those two mRNAs.