REGULATION BY GROWTH-FACTORS (IGF-I, B-FGF AND TGF-BETA) OF PROTOONCOGENE MESSENGER-RNA, GROWTH AND DIFFERENTIATION OF BOVINE ADRENOCORTICAL FASCICULATA CELLS

Nuclear proto-oncoproteins have been implicated in the regulation of gene expression by peptidic hormones and growth factors during cell proliferation and differentiation. In the present study we have investigated in bovine adrenal cells (BAC) the effects of basic fibroblast growth factor (b-FGF), insulin-like growth factor I (IGF-I) and transforming growth factor beta (TGF-beta) on c-jun, jun-B and c-fos mRNA levels and on cell growth and differentiation. Factors able to enhance the three proto-oncogenes (IGF-1, b-FGF and angiotensin II (A-II)) stimulate cell growth, whereas those inhibiting cell growth (TGF-beta and ACTH) decrease c-jun mRNA level. These results suggest that expression of c-jun may be required to induce cell proliferation. The relation between proto-oncogenes and the expression of differentiated functions appears to be more complex. Whereas IGF-I, b-FGF and A-II increase the three nuclear proto-oncogenes, the effects of IGF-I and b-FGF on cytochrome P450 17alpha-hydroxylase mRNA levels are opposite to those of A-II. On the other hand, while TGF-beta and A-II have inhibitory effects on P450 17alpha mRNA level, they have opposite effects on c-jun mRNA.