| Project/Area Number |
20591942
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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 |
Obstetrics and gynecology
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| Research Institution | Shinshu University |
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Principal Investigator |
KIKUCHI Norihiko Shinshu University, 医学部・附属病院, 助教 (50447728)
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| Co-Investigator(Kenkyū-buntansha) |
HORIUCHI Akiko 信州大学, 医学部, 講師 (80334895)
FUSEYA Chiho 信州大学, 医学部・附属病院, 助教(診療) (50447736)
SHIOZAWA Tanri 信州大学, 医学部, 教授 (20235493)
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| Project Period (FY) |
2008 – 2011
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 卵巣癌 / 脱メチル化 / S100A4 / S100A |
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| Research Abstract |
The S100A4 protein which belongs to calcium binding S100 protein family has been suggested to be linked to metastatic phenotypes of cancer cell. In this study, we investigated the association between the expression of S100A4 and hypomethylation of the S100A4 first intron in ovarian carcinoma cells. We first used immunohistochemistry to examine the expression and localization of S100A4 in 113 epithelial ovarian neoplasms and analyzed its prognostic significance in patients with ovarian carcinoma. Ovarian carcinoma patients with strong nuclear S100A4 expression showed a significantly shorter survival than those without (p=0.0045). Three ovarian cancer cell lines (SKOV3, A2780, A2780/CDDP) expressed S100A4, however, OVCAR3 and OSEs did not. Matrigel invasion assay showed that the expression level of S100A4 was associated with invasive ability in ovarian cancer cells. The specific siRNA for S100A4 suppressed S100A4 expression and the invasiveness of A2780/CDDP cells. We then studied the relationship between DNA methylation status and S100A4 expression by bisulfite-modified DNA sequencing in ovarian cancer cell lines and 51 cases of ovarian carcinoma tissues. We found that CpG sites in the first intron of the S100A4 gene were hypomethylated in S100A4 positive ovarian carcinoma cells. In contrast, these CpG sites were methylated in S100A4 negative ovarian carcinoma cells and S100A4 expression was altered by 5-aza-2deoxycytidine treatment. In ovarian cancer tissues, 24 cases of S100A4 strongly positive were hypomethylated in the first intron of S100A4 gene and 14 of all S100A4 negative cases were methylated.
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