CAMP INHIBITS IGF-I-INDUCED MITOGENESIS IN FETAL-RAT BROWN ADIPOCYTES- ROLE OF P21 RAS

Dibutyryl cAMP (DBcAMP) inhibited insulin-like growth factor I (IGF-I) -induced DNA synthesis of rat fetal brown adipocyte primary cultures. Its mitogenic inhibitory capacity, measured as [H-3]thymidine incorpor ation into acid-precipitable material, was dose-dependent, being maxim al at 0.5 mM. The entry of cells into 8 + G(2)/M phases of the cell cy cle and the increase in cell number induced by IGF-I were partially in hibited by DBcAMP at 24 h and totally prevented at 48 h. DBcAMP inhibi ted the mRNA expression of c-myc induced by IGF-I at 2 h. Moreover, DB cAMP inhibited in parallel H-ras mRNA expression, p21 ras, and prolife rating cellular nuclear antigen protein content induced by IGF-I at 24 and 48 h of culture, respectively, suggesting the involvement of p21 ras in the progression of fetal brown adipocytes through the 8 phase o f the cell cycle and DNA synthesis. (C) 1995 Academic Press, Inc.