title: Promoter methylation status of tumor suppressor genes and inhibition of expression of DNA methyltransferase 1 in non-small cell lung cancer.
abstract: DNA methylation is an epigenetic DNA modification catalyzed by DNA methyltransferase 1 (DNMT1). The purpose of this study was to investigate DNMT1 gene and protein expression and the effects of methylation status on tumor suppressor genes in human non-small cell lung cancer (NSCLC) cell lines grown in vitro and in vivo Human lung adenocarcinoma cell lines, A549 and H838, were grown in vitro and inoculated subcutaneously into nude mice to form tumors and were then treated with the DNA methylation inhibitor, 5-aza-2'-deoxycytidine, with and without treatment with the benzamide histone deacetylase inhibitor, entinostat (MS-275). DNMT1 protein expression was quantified by Western blot. Promoter methylation status of tumor suppressor genes (RASSF1A, ASC, APC, MGMT, CDH13, DAPK, ECAD, P16, and GATA4) was evaluated by methylation-specific polymerase chain reaction. Methylation status of the tumor suppressor genes was regulated by the DNMT1 gene, with the decrease of DNMT1 expression following DNA methylation treatment. Demethylation of tumor suppressor genes (APC, ASC, and RASSF1A) restored tumor growth in nude mice. The results of this study support a role for methylation of DNA as a potential epigenetic clinical biomarker of prognosis or response to therapy and for DNMT1 as a potential therapeutic target in NSCLC.
authors.affiliation: Thoracic Surgery, The Second Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541199, China.
authors.forename: Bangqing
authors.initials: B
authors.lastname: Liu
authors.affiliation: Thoracic Surgery, The Second Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541199, China.
authors.forename: Jianfei
authors.initials: J
authors.lastname: Song
authors.affiliation: Thoracic Surgery, Henan Provincial Chest Hospital, Zhengzhou, Henan 450000, China.
authors.forename: Jiaqiang
authors.initials: J
authors.lastname: Luan
authors.affiliation: Cardiothoracic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541001, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Sun
authors.affiliation: Thoracic Surgery, The Second Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541199, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Bai
authors.affiliation: Cardiothoracic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541001, China.
authors.forename: Haiyong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Cardiothoracic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541001, China.
authors.forename: Angui
authors.initials: A
authors.lastname: Li
authors.affiliation: Thoracic Surgery, The Second Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541199, China.
authors.forename: Lifei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Cardiothoracic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541001, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Feng
authors.affiliation: Thoracic Surgery, The Second Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541199, China duzhenzong@sina.com.
authors.forename: Zhenzong
authors.initials: Z
authors.lastname: Du
mesh_terms: D000818:Animals; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics*; D019175:DNA Methylation; D000077209:Decitabine; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D016147:Genes, Tumor Suppressor; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011401:Promoter Regions, Genetic; D011725:Pyridines / Q000494:pharmacology
chemical_list: D001549:Benzamides; D014408:Biomarkers, Tumor; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D011725:Pyridines; C118739:entinostat; D000077209:Decitabine; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human; C000619381:Dnmt1 protein, mouse; D001374:Azacitidine
keywords: DNA methylation; DNA methyltransferase 1; epigenetic; histone deacetylase; non-small cell lung cancer; tumor suppressor gene