Epithelial-mesenchymal transition and autophagy of hepatoma cells by the microenvironment change

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590983
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Nagasaki University
• Principal Investigator: NAKAO Kazuhiko 長崎大学, 医歯薬学総合研究科(医学系), 教授 (00264218)
• Co-Investigator(Kenkyū-buntansha): MIYAAKI Hisamitsu 長崎大学, 病院(医学系), 助教 (20437891)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 肝癌細胞 / インスリン / 分岐鎖アミノ酸 / VEGF / 上皮間葉移行

Outline of Final Research Achievements

We analyzed the expression of vascular endothelial growth factor (VEGF) in human hepatomacells under high-insulin culture conditions, and examined the effect of branched-chain amino acid (BCAA) on VEGF expression. VEGF secretion was significantly increased by 200 nM of insulin under BCAA deficient conditions, but it was repressed by the addition of BCAA. BCAA activated the mTOR pathway and increase HIF-1α expression under high-insulin culture conditions, however quantitative PCR analysis showed that insulin-induced expression of VEGF mRNAs decreased 2 h after the addition of BCAA. The half-lives of VEGF mRNAs were shortened in the presence of BCAA compared to the absence of BCAA. Therefore it is thought that BCAA regulate VEGF expression mainly at the post-transcriptional level. All three BCAA components(valine, Leucine, and Isoleucine) were required for acceleration of insulin-induced VEGF mRNA degradation.

Free Research Field

消化器内科学