Interaction of TPA and ultraviolet B radiation in regulation of ODC gene expression in rat keratinocytes

C. F. Rosen, D. Gajic, Q. Jia and D. J. Drucker Department of Medicine, University of Toronto, Ontario, Canada. Ultraviolet B radiation (UVB) and phorbol esters are known to promote tumor formation in skin; however, the interaction between UVB and phorbol esters in the regulation of gene expression remains incompletely understood. To define the interaction of UVB and phorbol esters in the control of keratinocyte gene expression, we have studied the effects of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) and UVB on the regulation of ornithine decarboxylase (ODC) gene expression in a rat keratinocyte cell line. Both UVB and TPA alone increased ODC activity and induced the expression of the ODC gene. The combination of UVB and TPA produced a further increment in ODC gene expression at 12 h, but UVB markedly attenuated the TPA induction of ODC mRNA transcripts at 3 h. Protein synthesis inhibition with cycloheximide also induced ODC mRNA transcripts, but did not eliminate the further induction of ODC gene expression by UVB or TPA. No changes in actin gene expression following exposure to TPA/UVB were detected in the same experiments. UVB and TPA alone or in combination had no effect on the transcriptional activity of an ODC-chloramphenicol acetyltransferase fusion gene in transfected rat keratinocytes. The results of these studies suggest a complex posttranscriptional interaction of phorbol esters and UVB in the control of keratinocyte gene expression.