Expression of growth arrest-specific (gas) genes in senescent murine cells.

The growth arrest-specific (gas) genes were initially identified on the basis of their preferential expression in mouse fibroblasts during quiescence, followed by down-regulation upon reentry into the cell cycle. We here report studies on the expression of these genes in murine fibroblasts undergoing replicative senescence in vitro. Our results indicate a different behavior between senescent and GO-arrested quiescent fibroblasts. Expression of the gas1 and 6 genes was dramatically reduced in senescent cells. Only basal levels of gas2, 3, and 5 genes were detected in senescent fibroblasts, and they were independent of the growing conditions of the cultures. Down-regulation of the gas1 gene expression in senescent cells was apparently due to reduced transcription of the gas1 gene. This correlates with an altered pattern of factors that bind to the promoter region of the gas1 gene, as measured by band shift assay with nuclear extracts of senescent fibroblasts.