title: Impact of DNA demethylation of the G0S2 gene on the transcription of G0S2 in squamous lung cancer cell lines with or without nuclear receptor agonists.
abstract: We recently identified that DNA methylation of the G0S2 gene was significantly more frequent in squamous lung cancer than in non-squamous lung cancer. However, the significance of G0S2 methylation levels on cancer cells is not yet known. We investigated the effect of G0S2 methylation levels on cell growth, mRNA expression, and chromatin structure using squamous lung cancer cell lines and normal human bronchial epithelial cells. DNA methylation and mRNA expression of G0S2 were inversely correlated, and in one of the squamous lung cancer cell lines, LC-1 sq, G0S2 was completely methylated and suppressed. Overexpression of G0S2 in LC-1 sq did not show growth arrest or apoptosis. The G0S2 gene has been reported to be a target gene of all-trans retinoic acid and peroxisome proliferator-activated receptor agonists. We treated LC-1 sq with 5-Aza-2'-deoxycytidine, Trichostatin A, all-trans retinoic acid, Wy 14643, or Pioglitazone either alone or in combination. Only 5-Aza-2'-deoxycytidine restored mRNA expression of G0S2. Chromatin immunoprecipitation revealed that histone H3 lysine 9 was methylated regardless of DNA methylation or mRNA expression. In summary, mRNA expression of G0S2 was regulated mainly by DNA methylation in squamous lung cancer cell lines. When the G0S2 gene was methylated, nuclear receptor agonists could not restore mRNA expression of G0S2 and did not show any additive effect on mRNA expression of G0S2 even after the treatment with 5-Aza-2'-deoxycytidine.
authors.affiliation: Department of General Thoracic Surgery, The University of Tokyo Hospital, Bunkyo-ku Hongo 7-3-1, Tokyo 113-8655, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Kusakabe
authors.forename: Kousuke
authors.initials: K
authors.lastname: Watanabe
authors.forename: Noriko
authors.initials: N
authors.lastname: Emoto
authors.forename: Naomi
authors.initials: N
authors.lastname: Aki
authors.forename: Hidenori
authors.initials: H
authors.lastname: Kage
authors.forename: Takahide
authors.initials: T
authors.lastname: Nagase
authors.forename: Jun
authors.initials: J
authors.lastname: Nakajima
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yatomi
authors.forename: Nobuya
authors.initials: N
authors.lastname: Ohishi
authors.forename: Daiya
authors.initials: D
authors.lastname: Takai
mesh_terms: D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D018797:Cell Cycle Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors; D000077209:Decitabine; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D008175:Lung Neoplasms / Q000235:genetics*; D018307:Neoplasms, Squamous Cell / Q000235:genetics*; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists / Q000378:metabolism*; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000494:pharmacology; D014158:Transcription, Genetic; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D018797:Cell Cycle Proteins; C508073:G0S2 protein, human; D006877:Hydroxamic Acids; D047492:Peroxisome Proliferator-Activated Receptors; D045162:Thiazolidinediones; C012589:trichostatin A; D014212:Tretinoin; D000077209:Decitabine; D015254:DNA Modification Methylases; D001374:Azacitidine; D000077205:Pioglitazone