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