Oncogenes modulate cellular gene expression and repress glucocorticoid regulated gene transcription.
The v-mos oncogene was subjected to the transcriptional control of the MMTV LTR and introduced by transfection into NIH 3T3 cells. The LTR v-mos gene was induced by the addition of glucocorticoid hormone to the growth medium of cells synchronized by culturing in 1.5% FCS for 36 h. The effects of p37 v-mos expression were monitored. The endogenous c-myc gene is induced as a consequence of p37 v-mos expression in a transient fashion, reaching a maximum of expression after 8 h. Induction of the c-myc gene was observed at the level of its transcriptional rate and at the level of mRNA concentration. Ornithine decarboxylase (ODC) mRNA was induced constitutively and high levels were found 8 and 25 h after v-mos induction. H4 histone mRNA is elevated at 25 h after hormone addition at a time when the mitogenic stimulus of v-mos causes DNA synthesis. The expression of actin mRNA is not affected by the v-mos oncogene. We have previously described a modulation of glucocorticoid dependent gene expression by oncogenes. In an extension of these observations the consequences of expression of the v-mos and the v-ras oncogenes were also studied in retrovirally infected NIH 3T3 cells. MMTV LTR constructs transfected into the infected cells could only be transiently induced by glucocorticoid hormone. The presence of the p37 v-mos and the p21 v-ras oncoproteins causes a repression of glucocorticoid hormone dependent gene transcription.
Jaggi
R
R
Ludwig Institute for Cancer Research, Inselspital, Bern, Switzerland.
Friis
R
R
Groner
B
B
D000199:Actins / Q000235:genetics*; D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology; D006657:Histones / Q000235:genetics*; D051379:Mice; D009857:Oncogenes; D009955:Ornithine Decarboxylase / Q000235:genetics*; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid; D014158:Transcription, Genetic
D000199:Actins; D005938:Glucocorticoids; D006657:Histones; D012333:RNA, Messenger; D009955:Ornithine Decarboxylase