Enhanced proliferation of human fibroblasts, in the presence of dexamethasone, is accompanied by changes in p21Waf1/Cip1/Sdi1 and the insulin-like growth factor type 1 receptor.
The addition of dexamethasone (dex) to human fibroblast cultures has been found to elicit enhanced proliferation. This enhancement is manifested by an increase in the initial growth rate, saturation density, and proliferative life span of WI-38 fibroblast cultures grown in the presence of dex. We examined the acute effects of dex on a number of growth-related genes in WI-38 cells. Our results show a decrease in the level of the cyclin-dependent kinase inhibitor p21Waf1/Cip1/sdi1 in response to dex. In addition, the level of the insulin-like growth factor type 1 receptor (IGF-1R) is increased in dex-treated cells. These changes are correlated with changes in the activity of the p21waf1/Cip1/Sdi1 and IGF-1R promoters. The results presented in this report suggest that dex may delay growth arrest in response to contact inhibition, as well as during cellular senescence. Thus, dex may act at multiple levels to enhance cellular proliferation in WI-38 cells: first, to decrease the level of an inhibitor of cell-cycle progression, and second, to increase the sensitivity of WI-38 cells to the proliferative effects of IGF-1. These acute effects may cooperate with other, as yet uncharacterized effects, to result in the enhanced proliferation seen in the presence of dex.
Li
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S
Center for Gerontological Research, Allegheny University of the Health Sciences, Philadelphia, Pennsylvania 19129, USA.
Mawal-Dewan
M
M
Cristofalo
V J
VJ
Sell
C
C
D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000187:drug effects* / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D017451:Receptors, Somatomedin / Q000187:drug effects* / Q000235:genetics
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D005938:Glucocorticoids; D012333:RNA, Messenger; D017451:Receptors, Somatomedin; D007334:Insulin-Like Growth Factor I; D003907:Dexamethasone