| ○種別 (必須): | □ | 著書
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| ○言語 (必須): | □ | 英語
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| ○招待 (推奨): |
| ○審査 (推奨): |
| ○カテゴリ (推奨): |
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| ○学究種別 (推奨): |
| ○組織 (推奨): |
| ○著者 (必須): | 1. | (英) Matsumura Satoshi (日) (読)
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| 2. | 井本 逸勢
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| 3. | (英) Kozaki Ken-ichi (日) (読)
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| 4. | (英) Matsui Takeshi (日) (読)
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| 5. | (英) Muramatsu Tomoki (日) (読)
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| 6. | (英) Furuta Mayuko (日) (読)
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| 7. | (英) Tanaka Shinji (日) (読)
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| 8. | (英) Sakamoto Michiie (日) (読)
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| 9. | (英) Arii Shigeki (日) (読)
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| 10. | (英) Inazawa Johji (日) (読)
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| ○題名 (必須): | □ | (英) Integrative array-based approach identifies MZB1 as a frequently methylated putative tumor-suppressor in hepatocellular carcinoma. (日)
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| ○副題 (任意): |
| ○要約 (任意): | □ | (英) The aim of this study was the identification of novel tumor suppressor genes (TSG) silenced by DNA hypermethylation in hepatocellular carcinoma (HCC). We conducted integrative array-based approach for genome-wide screening of methylation targets using a methylated DNA immunoprecipitation-CpG island microarray and expression array in three universal hepatoma cell lines and normal liver tissue. Through detailed expression and functional analyses using hepatoma cell lines and primary HCC samples, we isolated novel TSGs for HCC. A total of 642 genes were identified as methylated in three hepatoma cell lines but unmethylated in normal liver tissue, whereas 204 genes on autosomes were identified as genes unexpressed but restored after treatment with 5-aza-2'-deoxycytidine in these cell lines and expressed in normal tissue. Through the integration of results of the two-array analyses and further validation analyses of expression and methylation status in 17 cell lines and 30 primary tumors of hepatoma, we identified MZB1, marginal zone B and B1 cell-specific protein, encoding an endoplasmic reticulum protein, as a putative TSG frequently methylated within its CpG island in hepatoma. Among 162 patients with primary HCC, silencing of MZB1 protein was significantly and independently associated with a worse outcome. Restoration of MZB1 expression in hepatoma cells reduced cell proliferation in vitro and in vivo through G(1)-arrest. These results suggest that methylation-mediated silencing of MZB1 expression leads to loss of its tumor-suppressive activity, which may be a factor in the hepatocarcinogenesis, and is a useful prognosticator in HCC. (日)
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| ○キーワード (推奨): | 1. | (英) Animals (日) (読)
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| 2. | (英) Carcinoma, Hepatocellular (日) (読)
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| 3. | (英) Cell Line, Tumor (日) (読)
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| 4. | (英) Cell Proliferation (日) (読)
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| 5. | (英) Cell Transformation, Neoplastic (日) (読)
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| 6. | 細胞質分裂 (cytokinesis)
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| 7. | (英) DNA Methylation (日) (読)
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| 8. | 女性 (female)
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| 9. | (英) Gene Expression Profiling (日) (読)
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| 10. | (英) Gene Expression Regulation, Neoplastic (日) (読)
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| 11. | (英) Gene Silencing (日) (読)
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| 12. | (英) Genome-Wide Association Study (日) (読)
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| 13. | (英) Humans (日) (読)
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| 14. | (英) Kaplan-Meier Estimate (日) (読)
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| 15. | (英) Liver Neoplasms (日) (読)
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| 16. | (英) Mice (日) (読)
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| 17. | (英) Mice, SCID (日) (読)
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| 18. | (英) Neoplasm Transplantation (日) (読)
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| 19. | (英) Oligonucleotide Array Sequence Analysis (日) (読)
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| 20. | (英) Proportional Hazards Models (日) (読)
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| 21. | (英) Sequence Analysis, DNA (日) (読)
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| 22. | (英) Tumor Suppressor Proteins (日) (読)
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| ○発行所 (必須): |
| ○誌名 (任意): | □ | Clinical Cancer Research ([American Association for Cancer Research])
(pISSN: 1078-0432, eISSN: 1557-3265)
| ○ISSN (任意): | □ | 1078-0432
ISSN: 1078-0432
(pISSN: 1078-0432, eISSN: 1557-3265) Title: Clinical cancer research : an official journal of the American Association for Cancer ResearchTitle(ISO): Clin Cancer ResPublisher: American Association for Cancer Research (NLM Catalog)
(Scopus)
(CrossRef)
(Scopus information is found. [need login]) | [継承] |
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| ○巻 (任意): | □ | 18
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| ○号 (任意): | □ | 13
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| ○頁 (任意): | □ | 3541 3551
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| ○都市 (必須): |
| ○年月日 (必須): | □ | 西暦 2012年 5月 9日 (平成 24年 5月 9日)
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| ○URL (任意): |
| ○DOI (任意): | □ | 10.1158/1078-0432.CCR-11-1007 (→Scopusで検索)
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| ○PMID (任意): | □ | 22573353 (→Scopusで検索)
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| ○CRID (任意): |
| ○WOS (任意): |
| ○Scopus (任意): | □ | 2-s2.0-84863314557
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| ○評価値 (任意): |
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| ○指導教員 (推奨): |
| ○備考 (任意): | 1. | (英) Article.ELocationID: 10.1158/1078-0432.CCR-11-1007 (日)
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| 2. | (英) Article.Affiliation: Department of Molecular Cytogenetics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan. (日)
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| 3. | (英) Article.PublicationTypeList.PublicationType: Journal Article (日)
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| 4. | (英) Article.PublicationTypeList.PublicationType: Research Support, Non-U.S. Gov't (日)
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