Characterization of late response genes sequentially expressed during renewed growth of fibroblastic cells.

Many proto-oncogenes are rapidly and transiently activated during the early stages of the cellular transition from a resting G0 state to the DNA synthesis (S) phase. To get better understanding of the gene complexity involved at later stages, we isolated, by cDNA cloning, and identified 17 genes that are activated sequentially during the period of time from proto-oncogene expression to the onset of DNA synthesis in the hamster CCL39 fibroblastic cell line. When protein synthesis is inhibited, induced expression of these genes is unaffected for 10 of them, enhanced for four, in a fashion similar to the immediate-early response genes, and inhibited for three, as observed for delayed early-response genes. In addition to rhoG, a new member of the ras homolog gene family (Vincent et al., 1992), cDNA sequencing indicated that six of them correspond to cytoskeletal proteins (alpha-tubulin, vascular alpha-actin and skeletal gamma-actin), extracellular matrix protein (thrombospondin), secreted protease (plasminogen activator inhibitor-1) and energy-linked transporter (mitochondrial proton/phosphate symporter). This overall survey shows that numerous differentially regulated gene activations are associated with the cell cycle progression, and suggests that proteins involved in cellular reshaping participate actively in the control of cellular growth.