2010 Fiscal Year Final Research Report
Mechanistic analysis on DNA methylation in colorectal cancer and its application to diagnosis and therapy
| Project/Area Number |
20390353
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Kanazawa University |
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Principal Investigator |
KAWAKAMI Kazuyuki Kanazawa University, がん研究所, 准教授 (00293358)
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| Co-Investigator(Kenkyū-buntansha) |
MINAMOTO Toshinari 金沢大学, がん研究所, 教授 (50239323)
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| Co-Investigator(Renkei-kenkyūsha) |
SOGA Tomoyoshi 慶應義塾大学, 環境情報学部, 教授 (60338217)
ISHIGAKI Yasuhito 金沢医科大学, 総合医学研究所, 講師 (20232275)
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| Project Period (FY) |
2008 – 2010
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| Keywords | 大腸がん / メチル化 / 抗がん剤 |
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| Research Abstract |
We investigated the clinical value of methylation profile for the prognosis of colorectal cancer (CRC) and for the survival benefit from adjuvant chemotherapy with oral fluoropyrimidines. CpG island methylator phenotype (CIMP) was relatively rare in Japan and its clinical value is limited. In contrast, methylation of long interspersed nuclear element-1 (LINE-1) was a potential predictive marker for survival benefit from adjuvant chemotherapy with oral fluoropyrimidines in CRC patients. CRC cell lines treated with 5-FU showed increased expression of LINE-1 mRNA. This was associated with upregulation of the phospho-histone H2A. X in cells with low LINE-1 methylation, but not in cells with high LINE-1 methylation. The 5-FU-mediated induction of phospho-histone H2A. X, a marker of DNA damage, was inhibited by knockdown of LINE-1. These findings could be important for achieving personalized chemotherapy.
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