Regulation of EGR-1, c-jun, and c-myc gene expression by oncostatin M.
Oncostatin M (OM) is a cytokine that shares a structural and functional relationship with interleukin 6, leukemia-inhibitory factor, and granulocyte colony-stimulating factor. In this report, we tested for correlations between immediate-early gene expression and some of the cellular responses elicited by OM. We determined that OM stimulated a rapid and transient elevation of EGR-1, c-jun, and c-myc mRNA in human fibroblasts prior to their proliferation. OM also stimulated a transient induction of these genes in M1 leukemic cells that differentiated into nonreplicating, macrophage-like cells. The expression of c-myc, however, decreased significantly as the cells stopped dividing. Interestingly, OM had no detectable effect on the expression of EGR-1, c-jun, and c-myc during the cell cycle arrest of human A375 melanoma cells. Our results indicate that an early nuclear event associated with OM action is the regulation of immediate-early gene expression. We suggest that the transcription factors encoded by the EGR-1, c-jun, and c-myc genes are utilized in both cell proliferation and differentiation but are not part of the mechanism by which OM inhibits A375 cell growth.
Liu
J
J
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121.
Clegg
C H
CH
Shoyab
M
M
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D016758:Genes, jun / Q000187:drug effects* / Q000502:physiology; D016259:Genes, myc / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D051379:Mice; D053683:Oncostatin M; D010455:Peptides / Q000494:pharmacology*; D011493:Protein Kinase C / Q000502:physiology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D014407:Tumor Cells, Cultured
C508351:OSM protein, human; C508352:Osm protein, mouse; D010455:Peptides; D012333:RNA, Messenger; D053683:Oncostatin M; D011493:Protein Kinase C