| Project/Area Number |
12670487
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | OKAYAMA UNIVERSITY |
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Principal Investigator |
YUMOTO Yasuhiro OKAYAMA UNIVERSITY, RADIO-ISOTOPE CENTER, ASSOCIATE PROFESSOR, アイソトープ総合センター, 助教授 (30033369)
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| Co-Investigator(Kenkyū-buntansha) |
NOUSO Kazuhisa OKAYAMA UNIVERSITY, HOSPITAL, ASSISTANT, 医学部・附属病院, 助手 (10314668)
HIGASHI Toshihiro OKAYAMA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE AND DENTISTRY, ASSOCIATE PROFESSOR, 大学院・医歯学総合研究科, 助教授 (80173136)
HANAFUSA Tadashi OKAYAMA UNIVERSITY, RADIO-ISOTOPE CENTER, ASSISTANT, アイソトープ総合センター, 助手 (00228511)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2001: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Hepatocellular carcinoma / Hepatocarcinogenesis / cDNA micro array / LOH / Reduced expression of the IGFBP-3 / 癌部の遺伝子発現異常 / cDNA Microarray / IGFBP-3の発現低下 / HCC / メチル化 / IGFBP3 / methylation specific PC / microarray |
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| Research Abstract |
1) In order to disclose detailed genetic mechanisms in hepatocellular carcinoma (HCC) toward development of novel therapeuticf targets, we analyzed expression profiles of 22 primary (HCC) and their corresponding noncancerous tissues by means of cDNA micro arrays consisting of 1,176 genes (Atlas(TM) Human Cancer 1.2 cDNA expression array (Clontech Laboratoties, Inc., Palo Alto, CA)). Up-regulation of mitosis-promoting genes was observed in the majority of the tumors examined. The expression of 9 genes was enhanced 2 times or more in HCC cancerous tissue compared with noncancerous tissue in 5 or more of the 9 patients. In contrast, 8 genes were expressed at half the level or less in HCC cancerous tissue compared with noncancerous tissue. When standard clustering was performed to identify genes related to clinical phenotypes of the patients, 20 genes showed changes associated with the degree of differentiation of HCC. Thirteen of these genes were transcriptional factors or tissue-specific expression proteins related to cell deifferentiation or development. Our present analysis clarified a number of genes that characterize HCC. This information based on examination of clinical samples is considered to be useful for clarificfation of the mechanism of hepato-carcinogenesis and the diagnosis and treatment ot HCC.
2) Insulin-like growth factor binding proterin-3 (IGFBP-3) is postulated to be a mediator of growth suppression singnals. 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%) althoughn mutations were no 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-3functions like a tumor suppressor gene, it may be used as a therapeutic target for HCC.
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