Effect of benzo[a]pyrene diol epoxide on expression of retinoic acid receptor-beta in immortalized esophageal epithelial cells and esophageal cancer cells.
Expression of retinoic acid receptor-beta (RAR-beta) is frequently lost in tobacco-related cancers. Benzo[a]pyrene diol epoxide (BPDE) is an active metabolite of tobacco procarcinogen benzo[a]pyrene and plays an important role in tobacco carcinogenesis. We therefore exposed SV-40 immortalized esophageal epithelial cells and esophageal cancer cells to BPDE to understand possible interactions between BPDE and RAR-beta expression. Our data showed that BPDE decreased RAR-beta mRNA and protein levels by suppression of transcription of RAR-beta. Retinoic acid was able to partially block the inhibitory effect of BPDE on RAR-beta expression and to increase G1 phase of cell cycles. Furthermore, induction of COX-2 expression by BPDE was associated with RAR-beta inhibition. This study suggests that one way by which BPDE causes esophageal carcinogenesis may be through the inhibition of RAR-beta.
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Department of Clinical Cancer Prevention, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
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D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002461:Cell Line, Transformed; D051546:Cyclooxygenase 2; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D004947:Esophagus / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D011993:Recombinant Fusion Proteins; C082925:retinoic acid receptor beta; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D014212:Tretinoin; D008156:Luciferases; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases