Abstract
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.
Copyright 2001 Academic Press.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / pharmacology*
-
Cell Cycle / drug effects
-
Cell Line, Transformed
-
Cyclooxygenase 2
-
Epithelial Cells / drug effects*
-
Epithelial Cells / metabolism
-
Esophageal Neoplasms / genetics*
-
Esophageal Neoplasms / pathology
-
Esophagus / cytology
-
Esophagus / metabolism
-
Gene Expression Regulation / drug effects
-
Gene Expression Regulation, Enzymologic / drug effects
-
Humans
-
Isoenzymes / genetics
-
Luciferases / genetics
-
Luciferases / metabolism
-
Membrane Proteins
-
Prostaglandin-Endoperoxide Synthases / genetics
-
RNA, Messenger / drug effects
-
RNA, Messenger / genetics
-
RNA, Messenger / metabolism
-
Receptors, Retinoic Acid / genetics*
-
Recombinant Fusion Proteins / genetics
-
Recombinant Fusion Proteins / metabolism
-
Time Factors
-
Transcription, Genetic / drug effects
-
Tretinoin / pharmacology
-
Tumor Cells, Cultured
Substances
-
Isoenzymes
-
Membrane Proteins
-
RNA, Messenger
-
Receptors, Retinoic Acid
-
Recombinant Fusion Proteins
-
retinoic acid receptor beta
-
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide
-
Tretinoin
-
Luciferases
-
Cyclooxygenase 2
-
PTGS2 protein, human
-
Prostaglandin-Endoperoxide Synthases