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.
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.
Gaido
K W
KW
Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina 27709.
Maness
S C
SC
Leonard
L S
LS
Greenlee
W F
WF
D015152:Blotting, Northern; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D010957:Plasmids; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D016211:Transforming Growth Factor alpha / Q000096:biosynthesis* / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics
D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta; D003577:Cytochrome P-450 Enzyme System; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases