The Molecular mechanism of trastuzumab for gastric cancer via microRNA –gene pathway

2015 Fiscal Year Final Research Report

• Project/Area Number: 25462027
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kumamoto University
• Principal Investigator: IWATSUKI Masaaki 熊本大学, 大学院生命科学研究部(医), 助教 (50452777)
• 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)
• 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
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 胃癌 / トラスツズマブ耐性 / microRNA

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.

Free Research Field

微量癌細胞、抗癌剤耐性、microRNA