ENHANCED PROLIFERATION OF HUMAN FIBROBLASTS, IN THE PRESENCE OF DEXAMETHASONE, IS ACCOMPANIED BY CHANGES IN P21(WAF1 CIP1/SDI1) AND THE INSULIN-LIKE-GROWTH-FACTOR TYPE-1 RECEPTOR/

The addition of dexamethasone (dex) to human fibroblast cultures hss b een Found to elicit enhanced proliferation. This enhancement is manife sted by an increase in the initial growth rate, saturation density, an ti proliferative life span of WI-38 fibroblast cultures grown in the p resence of dex. We examined the acute effects of dex on a number of gr owth-related genes in WI-38 cells. Our results show a decrease in the level of the cyclin-dependent kinase inhibitor p21(Waf1/Cip1/Sdi1) in response to dex. In addition, the level of the insulin-like growth fac tor type 1 receptor (IGF-1R) is increased in dex-treated cells. These changes are correlated with changes in the activity of the p21(Waf1/Ci p1/Sdi1) and IGF-1R promoters. The results presented in this report su ggest that des may delay growth arrest in response to contact inhibiti on, as well as during cellular senescence. Thus, dex may act at multip le levels to enhance cellular proliferation in WI-38 cells: first, to decrease the level of an inhibitor of cell-cycle progression, and seco nd, to increase the sensitivity of WI-38 cells to the proliferative ef fects of IGF-1. These acute effects may cooperate with other, as yet u ncharacterized effects, to result in the enhanced proliferation seen i n the presence of des. (C) 1998 Wiley-Liss. Inc.