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 gas 1 and 6 genes was dramatically reduced in senescent cells. Only basal levels of gas 2, 3, and 5 genes were detected in senescent fibroblasts, and they were independent of the growing conditions of the cultures. Down-regulation of the gas 1 gene expression in senescent cells was apparently due to reduced transcription of the gas 1 gene. This correlates with an altered pattern of factors that bind to the promoter region of the gas 1 gene, as measured by band shift assay with nuclear extracts of senescent fibroblasts. (C) 1994 Academic Press, Inc.