Clarification of the microRNA pathway regulating resistance to Trastuzumab in gastric cancer

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461982
• 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: HAYASHI Naoko 熊本大学, 医学部附属病院, 非常勤診療医師 (20452899)
• Research Collaborator: ETO Kojiro 公益財団法人 がん研究会, その他部局等, 医員
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 胃癌 / トラスツズマブ / microRNA / 薬剤耐性

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.

Free Research Field

消化器外科