title: Reduced expression of insulin-like growth factor binding protein-3 and its promoter hypermethylation in human hepatocellular carcinoma.
abstract: Insulin-like growth factor binding protein-3 (IGFBP-3) is postulated to be a mediator of growth suppression signals. Reduced expression of the IGFBP-3 was observed in nine out of 12 human hepatocellular carcinomas (HCC) (75%). Promoter hypermethylation of the IGFBP-3 was detected in four out of 12 HCCs (33%) although mutations were not identified. The expression of IGFBP-3 was restored by the demethylating agent 5-aza-2'-deoxycytidine in HCC cell line with promoter hypermethylation (HepG2). As IGFBP-3 functions like a tumor suppressor gene, it may be used as a therapeutic target for HCC.
authors.affiliation: Isotope Center, Okayama University, Okayama University Medical School, 2-5-1 Shikata-cho, Okayama 700-8558, Japan. hanafusa@cc.okayama-u.ac.jp
authors.forename: Tadashi
authors.initials: T
authors.lastname: Hanafusa
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yumoto
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nouso
authors.forename: Harushige
authors.initials: H
authors.lastname: Nakatsukasa
authors.forename: Toru
authors.initials: T
authors.lastname: Onishi
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Fujikawa
authors.forename: Mayumi
authors.initials: M
authors.lastname: Taniyama
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Nakamura
authors.forename: Masayuki
authors.initials: M
authors.lastname: Uemura
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Takuma
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Yumoto
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Higashi
authors.forename: Takao
authors.initials: T
authors.lastname: Tsuji
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001483:Base Sequence; D015152:Blotting, Northern; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism*; D002897:Chromosomes, Human, Pair 7; D019175:DNA Methylation; D018076:DNA, Complementary / Q000378:metabolism; D000077209:Decitabine; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000096:biosynthesis* / Q000235:genetics*; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism*; D019656:Loss of Heterozygosity; D008360:Mannosephosphates / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011401:Promoter Regions, Genetic; D012313:RNA / Q000378:metabolism; D017527:Receptor, IGF Type 2 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D000964:Antimetabolites, Antineoplastic; D018076:DNA, Complementary; D018972:Insulin-Like Growth Factor Binding Protein 3; D008360:Mannosephosphates; D017527:Receptor, IGF Type 2; C027693:mannose-6-phosphate; D012313:RNA; D000077209:Decitabine; D001374:Azacitidine