2011 Fiscal Year Final Research Report
Ras/TGF-beta pathway downstream in liver metastasis of colorectal cancer
| Project/Area Number |
21591731
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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 |
Digestive surgery
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| Research Institution | Kitasato University |
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Principal Investigator |
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| Project Period (FY) |
2009 – 2011
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| Keywords | 大腸癌 / 肝転移 |
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| Research Abstract |
(Background) In colorectal cancer(CRC), K-ras mutation is found in nearly 40% of the patients, and it is of prognostic significance(Onozato W et al, J Surg Oncol, 2010). Moreover, its knockdown in CRC cell lines with mutated K-ras gene results in robust reduction of ability of cell proliferation and anchorage independent growth(Shirasawa S, Science, 1993), both of which reflect metastatic ability. On the other hand, robust alterations of glycan structures have been reported in CRC promotion steps, accompanied by remarkable phenotypic changes, however there is no report that mentions the relationship of K-ras mutation and glycan change.(Materials and Methods) We examined glycan change of CRC cell lines(DLD1 and HCT116) somatically knocked out for K-ras gene by lectin array including 41 lectins to elucidate whether K-ras mutation-induced glycan changes play a critical role in CRC promotion.(Result)(1) In DLD1, we compared DLD1wild type genotype cells(DLD1, DKS-5) with those that were knocked out for mutated K-ras gene(DKO-3, DKS-8), and the signals of MAL, MPA, UEA-I, and TJA-II were remarkably decreased in the knockdown cells.(2) In HCT116, we compared HCT116 wild type genotypic cells(HCT116, Hk2-10) with those that were knocked out for the mutated K-ras gene(Hke-3), and both MAL and MPA were remarkably declined.(3) In both cell lines, expression changes of glycans which can bind with MAL and MPA were consistent with the results of the lectin blotting, and both lectin signals were confirmed to be commonly altered by removing the mutated K-ras gene.(Conclusion) Mutated K-ras may be involved in critical phenotype change of CRC, accompanied by abnormal sialic acid recognition.
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Research Products
(14 results)
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[Presentation] 若年結腸癌におけるK-ras遺伝子変異の意義2010
Author(s)
小野里航, 山下継史, 中村俊隆, 大木暁, 鎌田弘樹, 小倉直人, 内藤正規, 池田篤, 小澤平太, 佐藤武郎, 井原厚, 渡邊昌彦
Organizer
第73回大腸癌研究会
Place of Presentation
鹿児島
Year and Date
2010-07-02
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[Presentation] 大腸癌におけるK-ras遺伝子変異と活性型EGFR(pEGFR)の予後との関連2009
Author(s)
小野里航, 山下継史, 中村隆俊, 大木暁, 加藤弘, 内藤正規, 旗手和彦, 小澤平太, 佐藤武郎, 井原厚, 渡邊昌彦
Organizer
第109回日本外科学会定期学術集会
Place of Presentation
福岡
Year and Date
2009-04-02
