title: Global DNA hypomethylation coupled to cellular transformation and metastatic ability.
abstract: Global DNA hypomethylation and DNA hypermethylation of promoter regions are frequently detected in human cancers. Although many studies have suggested a contribution to carcinogenesis, it is still unclear whether the aberrant DNA hypomethylation observed in tumors is a consequence or a cause of cancer. Here, we show that the enforced expression of Stella (also known as PGC7 and Dppa3) induced not only global DNA demethylation but also transformation of NIH3T3 cells. Furthermore, overexpression of Stella enhanced the metastatic ability of B16 melanoma cells, presumably through the induction of metastasis-related genes. These results provide new insights into the function of global DNA hypomethylation in carcinogenesis.
authors.affiliation: Department of Pathology, Osaka University, Osaka 565-0871, Japan; Department of General Thoracic Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Funaki
authors.affiliation: Nagahama Institute of Bio-Science and Technology, Shiga 526-0829, Japan; JST, CREST, Saitama 332-0012, Japan. Electronic address: tnakamura@nagahama-i-bio.ac.jp.
authors.forename: Toshinobu
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Department of Pathology, Osaka University, Osaka 565-0871, Japan.
authors.forename: Tsunetoshi
authors.initials: T
authors.lastname: Nakatani
authors.affiliation: Graduate School of Frontier Biosciences, Osaka University, Osaka 565-0871, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Umehara
authors.affiliation: Graduate School of Frontier Biosciences, Osaka University, Osaka 565-0871, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakashima
authors.affiliation: Department of General Thoracic Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
authors.forename: Meinoshin
authors.initials: M
authors.lastname: Okumura
authors.affiliation: Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Oboki
authors.affiliation: Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan.
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Saito
authors.affiliation: Department of Pathology, Osaka University, Osaka 565-0871, Japan; JST, CREST, Saitama 332-0012, Japan; Graduate School of Frontier Biosciences, Osaka University, Osaka 565-0871, Japan. Electronic address: tnakano@patho.med.osaka-u.ac.jp.
authors.forename: Toru
authors.initials: T
authors.lastname: Nakano
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology; D002868:Chromosomal Proteins, Non-Histone; D002999:Clone Cells; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009362:Neoplasm Metastasis / Q000473:pathology; D009368:Neoplasm Transplantation; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D047368:Tumor Burden
chemical_list: D002868:Chromosomal Proteins, Non-Histone; C466105:DPPA3 protein, human; D011506:Proteins; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D016283:Proto-Oncogene Proteins p21(ras)
keywords: DNA hypomethylation; Metastasis; Stella; Transformation