title: Ten-eleven translocation 1 functions as a mediator of SOD3 expression in human lung cancer A549 cells.
abstract: Superoxide dismutase (SOD) 3, one of the SOD isozymes, plays a pivotal role in extracellular redox homeostasis. The expression of SOD3 is regulated by epigenetics in human lung cancer A549 cells and human monocytic THP-1 cells; however, the molecular mechanisms governing SOD3 expression have not been elucidated in detail. Ten-eleven translocation (TET), a dioxygenase of 5-methylcytosine (5mC), plays a central role in DNA demethylation processes and induces target gene expression. In the present study, TET1 expression was abundant in U937 cells, but its expression was weakly expressed in A549 and THP-1 cells. These results are consistent with the expression pattern of SOD3 and its DNA methylation status in these cells. Moreover, above relationship was also observed in human breast cancer cells, human prostate cancer cells, and human skin fibroblasts. The overexpression of TET1-catalytic domain (TET1-CD) induced the expression of SOD3 in A549 cells, and this was accompanied by the direct binding of TET1-CD to the SOD3 promoter region. Furthermore, in TET1-CD-transfected A549 cells, the level of 5-hydroxymethylcytosine within that region was significantly increased, whereas the level of 5mC was decreased. The results of the present study demonstrate that TET1 might function as one of the key molecules in SOD3 expression through its 5mC hydroxylation in A549 cells.
authors.affiliation: a Laboratory of Clinical Pharmaceutics , Gifu Pharmaceutical University , Gifu , Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Kamiya
authors.affiliation: a Laboratory of Clinical Pharmaceutics , Gifu Pharmaceutical University , Gifu , Japan.
authors.forename: Risa
authors.initials: R
authors.lastname: Nakahara
authors.affiliation: a Laboratory of Clinical Pharmaceutics , Gifu Pharmaceutical University , Gifu , Japan.
authors.forename: Namiki
authors.initials: N
authors.lastname: Mori
authors.affiliation: a Laboratory of Clinical Pharmaceutics , Gifu Pharmaceutical University , Gifu , Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Hara
authors.affiliation: a Laboratory of Clinical Pharmaceutics , Gifu Pharmaceutical University , Gifu , Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Adachi
mesh_terms: D044503:5-Methylcytosine / Q000031:analogs & derivatives / Q000378:metabolism; D000072283:A549 Cells; D019175:DNA Methylation / Q000187:drug effects*; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D006899:Mixed Function Oxygenases / Q000235:genetics* / Q000378:metabolism; D010084:Oxidation-Reduction; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000096:biosynthesis* / Q000378:metabolism
chemical_list: D011518:Proto-Oncogene Proteins; C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D006899:Mixed Function Oxygenases; C462539:TET1 protein, human; C441642:SOD3 protein, human; D013482:Superoxide Dismutase
keywords: A549 cells; Superoxide dismutase 3; epigenetics; ten-eleven translocation 1