Fluorescent live-imaging of the switching of pyruvate kinase isoforms during tumorigenesis

2014 Fiscal Year Final Research Report

• Project/Area Number: 25640072
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: Miyagi Prefectural Hospital Organization Miyagi Cancer Center
• Principal Investigator: ITO SHIGEMI 地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), がん薬物療法研究部, 特任研究員 (80600006)
• Co-Investigator(Kenkyū-buntansha): TANUMA Nobuhiro 地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), がん薬物療法研究部, 主任研究員 (40333645) ; SATO Ikuro 地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), ティッシュバンクセンター, センター長 (50225918)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 代謝 / 解糖系 / ワールブルグ効果 / PKM / スプライシング

Outline of Final Research Achievements

Pyruvate kinase M (PKM) exists as two isoforms, M1 and M2, generated by alternative splicing. Expression of these isoforms switches from M1- to M2-type during tumorigenesis so that normal differentiated and proliferating/tumor cells express M1 and M2, respectively. In this study, a reporter-gene system, enabling us to visualize PKM-switch by cell-autonomous fluorescence, was developed. Using the reporter-gene, we generated transgenic mice, and examined those for lung tumor model. Unfortunately, any fluorescent signals except for auto-fluorescence were detected in tissues examined including tumor of the Tg-mice. More improvement(s) of the Tg-construct and/or alternative methods for introducing it into the mouse genome might be needed.

Free Research Field

腫瘍生物学