Regulation of EGR-1, c-jun, and c-myc Gene Expression by Oncostatin M

Abstrad Oncostatin M (OM) is a cytokine that shares a strudural and fundional relationship with interleukin 6, leukemia-inhibitory fador, and granuIocyte colonystimulating fador. 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 indudion of these genes in Ml 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 detedable effed on the expression of EGR-l, 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 adion is the regulation of immediate-early gene expression. We suggest that the transcription fadors encoded by the EGR-l, 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.