mos-induced inhibition of glucocorticoid receptor function is mediated by Fos

Activation of glucocorticoid hormone-dependent transcription involves the binding of the glucocorticoid hormone to its receptor followed by a specific interaction of the hormone/receptor complex with glucocorticoid responsive elements in the promoter region of hormone-inducible genes. In stably transfected NIH3T3 cells expressing the oncogene product of v-mos or fos, the expression from two glucocorticoid responsive promoters, MMTV LTR and metallothionein IIA (MtIIA), was shown to be impaired and was only transient. Cadmium-dependent MtIIA gene expression was not affected by the expression of v-mos in the cells. In transiently transfected NIH3T3 cells constitutive fos expression also inhibited glucocorticoid hormone-induced expression from the MMTV LTR. However, co-expression of antisense fos (here referred to as sof) inhibited the down-regulatory effect of Fos on glucocorticoid induced gene expression. v-mos expression in NIH3T3 cells induces fos mRNA and functional fos product (Fos) as reflected by its ability to induce expression of a transiently transfected AP-1 dependent reporter plasmid. We show that sof expression inhibits the down-regulatory effect of mos on expression of a transiently transfected pMMTV LTR-CAT. Our findings, thus, strongly suggest that the inhibition of glucocorticoid receptor function in cells expressing the v-mos oncogene is mediated by Fos.