Reduced expression of insulin-like growth factor binding protein-3 and its promoter hypermethylation in human hepatocellular carcinoma.
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.
Hanafusa
Tadashi
T
Isotope Center, Okayama University, Okayama University Medical School, 2-5-1 Shikata-cho, Okayama 700-8558, Japan. hanafusa@cc.okayama-u.ac.jp
Yumoto
Yasuhiro
Y
Nouso
Kazuhiro
K
Nakatsukasa
Harushige
H
Onishi
Toru
T
Fujikawa
Tatsuya
T
Taniyama
Mayumi
M
Nakamura
Shinichiro
S
Uemura
Masayuki
M
Takuma
Yoshitaka
Y
Yumoto
Eiichiro
E
Higashi
Toshihiro
T
Tsuji
Takao
T
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
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