Clarification of the microRNA pathway regulating resistance to Trastuzumab in gastric cancer
Project/Area Number |
26461982
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Digestive surgery
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Research Institution | Kumamoto University |
Principal Investigator |
HAYASHI Naoko 熊本大学, 医学部附属病院, 非常勤診療医師 (20452899)
|
Co-Investigator(Kenkyū-buntansha) |
石本 崇胤 熊本大学, 大学院生命科学研究部(医), 特任講師 (00594889)
馬場 祥史 熊本大学, 大学院生命科学研究部(医), 講師 (20599708)
岩槻 政晃 熊本大学, 大学院生命科学研究部(医), 助教 (50452777)
|
Research Collaborator |
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) |
2014-04-01 – 2017-03-31
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Project Status |
Completed (Fiscal Year 2016)
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Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
Keywords | 胃癌 / トラスツズマブ / microRNA / 薬剤耐性 / miR 223 / FBXW7 / MCL1 / c-Myc / c-Jun / HER2 / Trastuzumab / cisplatine / miR-21 / PTEN |
Outline of Final Research Achievements |
We established the Trastuzumab resistance gastric cancer (GC) cell line with continuous Trastuzumab administration. Parent GC cell line and resistance GC cell line are subjected to miR microarray. We identified miR-21 which can regulate PTEN and miR-223, which can regulate FBXW7, using miR array analysis using by resistance cell lines which we established. Overexpression of miR-21 decreased PTEN expression and the sensitivity of gastric cancer cells to Trastuzumab, while suppression of miR-21 restored PTEN expression and the sensitivity of GC cells to Trastuzumab. Similarly, Overexpression of miR-223 decreased FBXW7 expression and the sensitivity of gastric cancer cells to Trastuzumab, while suppression of miR-223 restored FBXW7 expression and the sensitivity of GC cells to Trastuzumab. Moreover, overexpression of miR-223 significantly suppressed Trastuzumab-induced apoptosis. These findings suggest that this pathway may be crucial to the mechanism of resistance to Trastuzumab in GC.
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Report
(4 results)
Research Products
(5 results)
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[Journal Article] The sensitivity of gastric cancer to trastuzumab is regulated by the miR-223/FBXW7 pathway2015
Author(s)
Eto K, Iwatsuki M, Watanabe M, Ishimoto T, Ida S, Imamura Y, Iwagami S, Baba Y, Sakamoto Y, Miyamoto Y, Yoshida N, Baba H
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Journal Title
Int J Cancer
Volume: 136(7)
Issue: 7
Pages: 1537-45
DOI
Related Report
Peer Reviewed
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[Journal Article] The microRNA-21/PTEN pathway regulates the sensitivity of HER2-positive gastric cancer cells to trastuzumab2014
Author(s)
Eto K, Iwatsuki M, Watanabe M, Ida S, Ishimoto T, Iwagami S, Baba Y, Sakamoto Y, Miyamoto Y, Yoshida N, Baba H
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Journal Title
Ann Surg Oncol
Volume: 21(1)
Issue: 1
Pages: 343-50
DOI
Related Report
Peer Reviewed
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