TRANSFORMING GROWTH-FACTOR BETA(1) INDUCES MITOGENESIS IN FETAL-RAT BROWN ADIPOCYTES

The presence of transforming growth factor beta(1) (TGF-beta(1)) for 2 4 or 48 h stimulated DNA synthesis, the percentage of cells in the S G(2)/M phases of the cell cycle, and cell number, as compared to quie scent cells. The mitogenic capacity of TGF-beta(1) (1 pM) was similar to that shown by 10% fetal calf serum (FCS). TGF-beta(1) for 48 h incr eased by 5-fold the percentage of eel Is containing (H-3)thymidine-lab eled nuclei as compared to quiescent cells. In addition, single fetal brown adipocytes, showing their typical multilocular fat droplets phen otype, become positive for (H-3)thymidine-labeled nuclei in response t o TGF-beta(1). Moreover, TGF-beta(1) induced the mRNA expression of a complete set of proliferation-related genes, such as c-fos (30 min), c -myc and beta-actin (2 h), and H-ras, cdc2 kinase, and glucose 6-phosp hate dehydrogenase (G6PD) at 4 and 8 h, as compared to quiescent cells . Concurrently, TGF-beta(1) for 12 h increased the protein content of proliferating cellular nuclear antigen (PCNA) by 6-fold and p21-ras by 2-fold. Although our results demonstrate that TGF-beta(1) induces the expression of very early genes related to cell proliferation, TGF-bet a(1) could be acting either as a mitogen or as a survival factor to in duce proliferation in fetal brown adipocytes. (C) 1996 Wiley-Liss, Inc .