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.
Touray
M
M
Department of Clinical and Experimental Cancer Research, University of Bern, Switzerland.
Ryan
F
F
Saurer
S
S
Martin
F
F
Jaggi
R
R
D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D015536:Down-Regulation; D016258:Genes, mos; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D011519:Proto-Oncogenes; D011965:Receptors, Glucocorticoid / Q000502:physiology*; D012091:Repetitive Sequences, Nucleic Acid; D014157:Transcription Factors / Q000378:metabolism
D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D011965:Receptors, Glucocorticoid; D014157:Transcription Factors; D002104:Cadmium; D003907:Dexamethasone