| Project/Area Number |
25462027
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Kumamoto University |
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Principal Investigator |
IWATSUKI Masaaki 熊本大学, 大学院生命科学研究部(医), 助教 (50452777)
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| Co-Investigator(Kenkyū-buntansha) |
WATANABE Masayuki 公益財団法人がん研究会, その他部局等, 食道担当部長 (80254639)
ISHIMOTO Takatsugu 熊本大学, 国際先端医学研究機構, 客員准教授 (00594889)
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| Research Collaborator |
KURASHIGE Junji 熊本大学, 医学部附属病院, 特任助教
ETO Kojiro 公益財団法人がん研究会, その他部局等, 医員
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 胃癌 / トラスツズマブ耐性 / microRNA / Trastuzumab耐性 / CGH array / マイクロアレイ / FBXW7 / microRNA array |
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| Outline of Final Research Achievements |
The aim of this study was to identify microRNA- gene pathway that regulates the sensitivity of HER2-positive GC cells to trastuzumab. We performed following experiments: (i) trastuzumab-resistant GC cell: We cultured the HER2-positive cell line in the presence of trastuzumab (ii) microRNA array: We examined the miR expression profile using miR array analysis. (iii) novel miR-gene pathway: We focused on miR-223-FBXW7 pathway based on miRarray analysis.
Results: (i) We established resistant cell without significant changes in HER2 in the presence of trastuzumab continuously for 6 months. (ii) We identified 23 miRs up-regulated in the resistant cells. (iii) the miR-223/FBXW7 pathway regulates the sensitivity of a HER2-positive GC cell line to trastuzumab. In conclusion, this study suggested that the miR-223-FBXW7 pathway can be a crucial clue to the mechanism of resistance to trastuzumab in GC.
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