The E1a gene prevents inhibition of keratinocyte proliferation by dexamethasone.
Glucocorticoids have inhibitory effects on the proliferation of several cell types. In this study, we found that dexamethasone, a synthetic steroid with glucocorticoid activity, inhibits proliferation of established mouse Pam 212 keratinocytes. Transfection with the adenoviral early region 1a (E1a) gene confers a strong resistance to the inhibition by dexamethasone. Two deletion E1a mutants, one whose product lacks the ability to bind the cellular proteins p60/p105/p107 and another that is unable to bind p300, were shown to induce a resistance similar to that associated with the intact E1a gene. These results differ from those previously observed with two other growth inhibitory signals, transforming growth factor beta 1 and adenosine 3',5'-cyclic monophosphate, in which the mutated E1a genes confer only partial or no resistance, indicating that a different mechanism mediates resistance against glucocorticoids.
Florin-Christensen
M
M
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510.
Missero
C
C
Dotto
G P
GP
Florin-Christensen
J
J
D017500:Adenovirus E1A Proteins / Q000235:genetics*; D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D003907:Dexamethasone / Q000494:pharmacology*; D005814:Genes, Viral; D015603:Keratinocytes / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D007700:Kinetics; D051379:Mice; D010957:Plasmids; D013936:Thymidine / Q000378:metabolism; D014162:Transfection
D017500:Adenovirus E1A Proteins; D005576:Colforsin; D003907:Dexamethasone; D004247:DNA; D013936:Thymidine