Glucocorticoid regulation of transcription of the c-myc cellular protooncogene in P1798 cells.

Abstract

Glucocorticoids regulate proliferation of lymphosarcoma P1798 in culture. Treatment with dexamethasone caused a redistribution of cells with respect to the cell cycle. A decrease in cells in S and G2 + M phases was observed. This was accompanied by a corresponding increase in G1 cells. Growth arrest was preceded by a rapid and precipitous decrease in the expression of the cellular c-myc gene. Restriction analysis of the c-myc gene indicated that this locus was neither amplified nor grossly rearranged in P1798 cells. Glucocorticoids caused a decrease in the abundance of c-myc mRNA. After 24 h in 0.1 microM dexamethasone, c-myc mRNA levels declined to less than 5% of control. Fifty percent inhibition occurred within 90 min. The effects of dexamethasone were completely reversible. The amount of c-myc mRNA returned to control levels within 4 h after withdrawal of the hormone. Nuclear run-on transcription analysis indicated that glucocorticoids regulate transcription of the c-myc gene in P1798 cells. Transcription of exons I and II was inhibited to the same extent, suggesting that glucocorticoids inhibit initiation of transcription. Inhibition of transcription may account for decreased expression of c-myc which may, in turn, account for the antiproliferative effects of the hormone.