TCDD suppression of tissue transglutaminase stimulation by retinoids in malignant human keratinocytes.
The human keratinocyte line SCC-4 is a model system in which to explore the mechanism by which 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) interferes with the action of hormones in the steroid receptor superfamily. In present work, retinoid induction of tissue transglutaminase mRNA was suppressed 60-70% by 10 nM TCDD in the human squamous carcinoma cell line SCC-4. This effect occurred without enhanced degradation of the mRNA and thus appeared to result from altered transcription. The actions of all-trans-retinoic acid and the synthetic retinoid TTNPB ((E)4-[2-(5,6,7,8-tetrahydro-5,5,8, 8-tetramethyl-2-naphthylenyl)-1propenyl] benzoic acid), which resists metabolic degradation, were suppressed to the same extent without obvious changes in their EC(50)s. In addition, TCDD suppression of reporter transcription, driven by a retinoic acid response element, was not evident in transient or stable transfections of SCC-4 cells. Sodium butyrate (3 mM) alone induced tissue transglutaminase and augmented retinoid induction. In the presence of butyrate, TCDD acted as an inducer and did not reduce retinoid stimulation. Retinoic acid induction of tissue transglutaminase displayed a lag phase of >24 h, indicating that the induction has an indirect component. Rather than depleting active retinoid in the culture medium or generally inactivating retinoid receptor function, TCDD may suppress retinoid action in this case by interfering with the late phase of induction.
Department of Environmental Toxicology, University of California, Davis 95616-8588, USA.
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D001565:Benzoates / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000201:enzymology; D006801:Humans; D015603:Keratinocytes / Q000201:enzymology; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D012333:RNA, Messenger / Q000032:analysis; D012176:Retinoids / Q000494:pharmacology*; D011503:Transglutaminases / Q000037:antagonists & inhibitors* / Q000235:genetics; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D001565:Benzoates; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D012176:Retinoids; D014212:Tretinoin; C038864:4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid; D011503:Transglutaminases