ArticleMolecular cancer2010
Benzo[a]pyrene diol epoxide suppresses retinoic acid receptor-beta2 expression by recruiting DNA (cytosine-5-)-methyltransferase 3A.
Article in Molecular cancer, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 32 citations in OpenAlex.
- Environmental Xenobiotics and Epigenetic Modifications: Implications for Human Health and Disease.Journal of xenobiotics · 2025Review
- The epigenetic landscape shapes smoking-induced mutagenesis by modulating DNA damage susceptibility and repair efficiency.Nucleic acids research · 2025Article
- Implications of petrochemical exposure and epigenetic alterations on human health.Frontiers in toxicology · 2025Review
- Smoke and Spike: Benzo[a]pyrene Enhances SARS-CoV-2 Infection by Boosting NR4A2-Induced ACE2 and TMPRSS2 Expression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Dynamic changes of DNA methylation induced by benzo(a)pyrene in cancer.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2023Review
- Demystifying the Functional Role of Nuclear Receptors in Esophageal Cancer.International journal of molecular sciences · 2022Review
- The relationship between P16Scientific reports · 2022Article
- Cigarette smoke extract promotes DNA methyltransferase 3a expression in dendritic cells, inducing Th-17/Treg imbalance via the c-Jun/allograft inflammatory factor 1 axis.The Kaohsiung journal of medical sciences · 2021Article
- Targeting Epigenetic Mechanisms in Vascular Aging.Frontiers in cardiovascular medicine · 2021Review
- Enhancement of tumor suppressor RAR-β protein expression by cationic liposomal-ATRA treatment in benzo(a)pyrene-induced lung cancer mice model.Naunyn-Schmiedeberg's archives of pharmacology · 2019Article
- A Tox21 Approach to Altered Epigenetic Landscapes: Assessing Epigenetic Toxicity Pathways Leading to Altered Gene Expression and Oncogenic Transformation In Vitro.International journal of molecular sciences · 2017Review
- Critical Points in Tumorigenesis: A Carcinogen-Initiated Phase Transition Analyzed via Single-Cell Proteomics.Small (Weinheim an der Bergstrasse, Germany) · 2016Article
- The detective, prognostic, and predictive value of DNA methylation in human esophageal squamous cell carcinoma.Clinical epigenetics · 2016Review
- Environmental factors and unhealthy lifestyle influence oxidative stress in humans--an overview.Environmental science and pollution research international · 2013Review
- Epigenetic, genetic and environmental interactions in esophageal squamous cell carcinoma from northeast India.PloS one · 2013Article
- Proteomic analysis of the marine diatom Thalassiosira pseudonana upon exposure to benzo(a)pyrene.BMC genomics · 2011Article
- Comparable molecular alterations in 4-nitroquinoline 1-oxide-induced oral and esophageal cancer in mice and in human esophageal cancer, associated with poor prognosis of patients.In vivo (Athens, Greece)Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Tobacco smoke is an important risk factor for various human cancers, including esophageal cancer. How benzo [a]pyrene diol epoxide (BPDE), a carcinogen present in tobacco smoke as well as in environmental pollution, induces esophageal carcinogenesis has yet to be defined. In this study, we investigated the molecular mechanism responsible for BPDE-suppressed expression of retinoic acid receptor-beta2 (RAR-beta2) in esophageal cancer cells. We treated esophageal cancer cells with BPDE before performing methylation-specific polymerase chain reaction (MSP) to find that BPDE induced methylation of the RAR-beta2 gene promoter. We then performed chromatin immunoprecipitation (ChIP) assays to find that BPDE recruited genes of the methylation machinery into the RAR-beta2 gene promoter. We found that BPDE recruited DNA (cytosine-5-)-methyltransferase 3 alpha (DNMT3A), but not beta (DNMT3B), in a time-dependent manner to methylate the RAR-beta2 gene promoter, which we confirmed by reverse transcription-polymerase chain reaction (RT-PCR) analysis of the reduced RAR-beta2 expression in these BPDE-treated esophageal cancer cell lines. However, BPDE did not significantly change DNMT3A expression, but it slightly reduced DNMT3B expression. DNA methylase inhibitor 5-aza-2'-deoxycytidine (5-Aza) and DNMT3A small hairpin RNA (shRNA) vector antagonized the effects of BPDE on RAR-beta2 expressions. Transient transfection of the DNMT3A shRNA vector also antagonized BPDE's effects on expression of RAR-beta2, c-Jun, phosphorylated extracellular signal-regulated protein kinases 1/2 (ERK1/2), and cyclooxygenase-2 (COX-2), suggesting a possible therapeutic effect. The results of this study form the link between the esophageal cancer risk factor BPDE and the reduced RAR-beta2 expression.
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