AJP - Cell Physiology, Vol 263, Issue 5 C1103-C1110, Copyright © 1992 by American Physiological Society
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.
