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J. Biol. Chem., Vol. 267, Issue 34, 24591-24595, Dec, 1992
KW Gaido, SC Maness, LS Leonard and WF Greenlee
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a potent modulator of
epithelial cell growth and differentiation, has been shown to induce
transforming growth factor (TGF)-alpha in cultures of human keratinocytes
and in the human keratinocyte cell line, SCC-12F. In this report, we
investigated the mechanisms by which TCDD alters TGF-alpha expression. In
addition, we studied the actions of TCDD on TGF-beta 1 and TGF-beta 2
expression. Treatment of SCC-12F cells with TCDD resulted in an increase in
TGF-alpha and a reduction in TGF-beta 2 mRNA levels while mRNA levels for
TGF-beta 1 were unchanged. Changes in TGF- alpha and TGF-beta 2 expression
were maximal by 24 h. No change in the rate of transcription of TGF-alpha
was detected following treatment with TCDD as determined by nuclear run-off
analysis. TCDD treatment resulted in a stabilization of TGF-alpha mRNA as
judged by an approximately 2-fold higher level of TGF-alpha mRNA in treated
versus control cells in the presence of actinomycin D. In contrast to TGF-
alpha, the rate of transcription of TGF-beta 2 was significantly reduced
following TCDD treatment. These findings demonstrate that the induction of
TGF-alpha expression in SCC-12F cells by TCDD occurs post-
transcriptionally, primarily by mRNA stabilization, while TGF-beta 2
expression is reduced due to a decrease in the rate of TGF-beta 2 gene
transcription.
2,3,7,8-Tetrachlorodibenzo-p-dioxin-dependent regulation of transforming growth factors-alpha and -beta 2 expression in a human keratinocyte cell line involves both transcriptional and post- transcriptional control
Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina 27709.
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