2013 Fiscal Year Final Research Report
Development of in vivo screening systems for cancer metastasis suppressors
| Project/Area Number |
24650627
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Tumor biology
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| Research Institution | 愛知県がんセンター(研究所) |
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Principal Investigator |
AOKI MASAHIRO 愛知県がんセンター(研究所), 分子病態学部, 部長 (60362464)
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| Co-Investigator(Kenkyū-buntansha) |
SAKUMA Keiichiro 愛知県がんセンター(研究所), 分子病態 学部, 主任研究員 (90402891)
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| Co-Investigator(Renkei-kenkyūsha) |
KOJIMA Yasushi 愛知県がんセンター(研究所), 分子病態 学部, 主任研究員 (30464217)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Keywords | 転移 / 大腸がん / shRNA |
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| Research Abstract |
Cancer metastasis is a complex process whose molecular mechanism is not fully understood. To identify targets for prevention and/or therapy of cancer metastasis, we developed a genome-wide shRNA library screen for colon cancer metastasis suppressor genes using an orthotopic transplantation mouse model. CMT93 cells, a murine colon cancer cell line with poor metastasizing activity, were transduced with lentiviral shRNA library and transplanted into the rectum of syngeneic C57/BL6 mice. The sequences encoding shRNA were retrieved from genomic DNA of the metastatic lesions by PCR for sequencing, followed by identification of the candidate genes targeted by the shRNA. Among 11 candidate genes identified so far, we focused on Hnrpll encoding an RNA-binding protein involved in pre-mRNA splicing, because the shRNA targeting the gene was identified from two metastatic lesions found in different transplanted mice. Knockdown of Hnrpll in CMT93 cells resulted in accelerated proliferation.
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