title: Ataxia-telangiectasia mutated expression is associated with tobacco smoke exposure in esophageal cancer tissues and benzo[a]pyrene diol epoxide in cell lines.
abstract: Esophageal cancer is a substantial health problem because of its usually late stage at diagnosis and poor prognosis. Tobacco smoking and alcohol use are the most important risk factors in the development of esophageal squamous cell carcinoma (SCC). Our previous study demonstrated the binding of benzo[a]pyrene diol epoxide (BPDE), a carcinogen present in tobacco smoke and environmental pollution, to the ataxia-telangiectasia mutated (ATM) gene. To understand how this binding affects the alteration of ATM expression and to identify biomarkers for the detection of esophageal cancer, we analyzed ATM mRNA expression in tissue specimens from patients with esophageal SCC and premalignant lesions using in situ hybridization. We then performed in vitro experiments to verify and extend our ex vivo observations. We found that ATM expression was increased in esophageal SCC and its premalignant lesions when compared with normal tissues and that increased ATM expression was associated with tobacco smoke exposure and tumor de-differentiation. Moreover, BPDE induced ATM expression in esophageal SCC cell lines in a time-dependent manner. In summary, the BPDE in tobacco smoke may be responsible for increased ATM expression in premalignant and malignant esophageal tissues. Our findings suggest that the ATM gene should be further evaluated as a biomarker for the early detection of esophageal cancer and tobacco use in patients.
authors.affiliation: Department of Pathology, Anhui Medical University, Hefei, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jiang
authors.forename: Zheng D
authors.initials: ZD
authors.lastname: Liang
authors.forename: Tsung T
authors.initials: TT
authors.lastname: Wu
authors.forename: Liyu
authors.initials: L
authors.lastname: Cao
authors.forename: Hongfu
authors.initials: H
authors.lastname: Zhang
authors.forename: Xiao-Chun
authors.initials: XC
authors.lastname: Xu
mesh_terms: D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000633:toxicity*; D064007:Ataxia Telangiectasia Mutated Proteins; D014408:Biomarkers, Tumor / Q000235:genetics; D015153:Blotting, Western; D002273:Carcinogens / Q000633:toxicity*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics*; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D017403:In Situ Hybridization; D011230:Precancerous Conditions / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D012907:Smoking; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D002273:Carcinogens; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases