EXPRESSION OF PROTOONCOGENES DURING LYMPHOCYTE-ACTIVATION BY GROWTH-FACTORS

Effects of growth factors of non-immune origin including somatotropin (ST) and platelet-derived growth factor (PDGF) on the expression of th e proteins encoded by c-fos, c-myc, c-fun, and c-ets family protooncog enes were studied for the first time. The dynamics of the oncoprotein expression in activated CD3+-lymphocytes was investigated by immunoblo tting. The accumulation of the Fos and Myc proteins was enhanced in T- lymphocytes treated with ST, PDGF, or phytohemagglutinin; the accumula tion was maximum at 30-60 min and decreased in 2 h; the data indicate that the oncoproteins participate in the early lymphocyte activation b y various growth factors. The Jun protein appears only in 3 h after th e onset of lymphocyte activation; this suggests independent participat ion of Fos in the early stages of lymphocyte activation prior to the a ppearance of Jun, preceding the joint action of Fos and Jun within the AP-1 transcription complex. The products of the c-ets family are diff erentially activated by the studied growth factors. Resting lymphocyte s actively accumulate the Ets-1 protein; ST and PDGF activation decrea ses Ets-1 expression in 2 h. The Ets-2 protein is not detected in rest ing cells and PDGF-activated lymphocytes, whereas lymphocyte activatio n by ST is associated with accumulation of Ets-2. The data suggest tha t the product of the c-ets-1 gene is more important in the regulation of resting cells and the product of the c-ets-2 gene is important duri ng activation of lymphocytes by ST. The results indicate that activati on of lymphocytes with growth factors of non-immune origin is mediated by several signal transduction pathways.