Effect of benzo[a]pyrene diol epoxide on expression of retinoic acid receptor-beta in immortalized esophageal epithelial cells and esophageal cancer cells

Biochem Biophys Res Commun. 2001 Mar 9;281(4):872-7. doi: 10.1006/bbrc.2001.4433.

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.

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