A novel early growth response gene rapidly induced by fibroblast, epithelial cell and lymphocyte mitogens.

Mitogens evoke many alterations in gene expression in eukaryotic cells. Genes which are activated rapidly and transiently, that are evolutionarily conserved and whose induction is shared by diverse cell types when exposed to different growth stimuli are likely to be of critical importance in transducing mitogenic signals and regulating cellular proliferation. c-myc and c-fos are the only known genes fulfilling these criteria. We report on the molecular cloning of a novel early growth response (egr) gene which also satisfies these conditions. In response to serum, its 3.7 kb mRNA is induced dramatically in mouse fibroblasts reaching a peak level at about 30 minutes that is ten times higher than the maximal value attained by c-fos mRNA. This transcript is induced by the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate and is "superinduced" by serum and cycloheximide together. Importantly, the gene is highly induced by different mitogens in a wide array of cell types: insulin stimulated rat hepatoma cells, adenosine diphosphate treated monkey kidney epithelial cells, and phytohemagglutinin stimulated human peripheral blood lymphocytes. Given the many properties that this gene shares with c-myc and c-fos, it may play a key role in the control of cell growth and perhaps in oncogenesis.