2016 Fiscal Year Final Research Report
Development of target therapy for microsatelite instability colorectal cancer
| Project/Area Number |
15K19892
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Digestive surgery
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| Research Institution | Higashihiroshima Medical Center |
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Principal Investigator |
Shimomura Manabu 独立行政法人国立病院機構東広島医療センター(臨床研究部), 診療部, 外科医師 (60457249)
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Keywords | colorectal cancer / microsatellite |
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| Outline of Final Research Achievements |
Mutations in TGFBR2 occur in high-frequency microsatellite instability (MSI-H) colorectal cancer (CRC). We generated CDX2P-19Cre;Apcflox/flox;Tgfbr2flox/flox mice, with simultaneous loss of Apc and Tgfbr2. These mice developed tumors, including adenocarcinoma in the proximal colon. We compared gene expression profiles between tumors of the two types of mice using microarray analysis. Our results showed that the expression of the murine homolog of GSDMC was significantly upregulated by 9.25-fold in tumors of DX2PG19Cre;Apcflox/flox;Tgfbr2flox/flox mice compared with those of CDX2P-G19Cre;Apcflox/flox mice. We then investigated the role of GSDMC in regulating CRC tumorigenesis. The silencing of GSDMC led to a significant reduction in the proliferation and tumorigenesis of CRC cell lines, whereas the overexpression of GSDMC enhanced cell proliferation. These results suggested that GSDMC functioned as an oncogene, promoting cell proliferation in colorectal carcinogenesis.
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| Free Research Field |
surgery
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