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Role of INPP4B in melanoma development: possible effects of 3-BP as promising anticancer drug

Research Project

Project/Area Number 26461679
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Dermatology
Research InstitutionAkita University

Principal Investigator

MANABE MOTOMU  秋田大学, 医学(系)研究科(研究院), 教授 (30138309)

Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsINPP4B / PTEN / PI3K / メラノーマ / 糖代謝 / 癌抑制遺伝子 / 遺伝子改変マウス
Outline of Final Research Achievements

INPP4B negatively regulates pi3-kinase signaling and is a tumor suppressor in some types of cancers. However, the role of INPP4B in the development of melanoma remains unclear. We therefore sought to investigate the tumor suppressive functions of INPP4B in vivo in knock-out KO mouse models. Here, we show that (1) Inpp4b null mice do not develop the tumorigenic phenotype of Pten haploinsufficient mice, (2) Inpp4b null mice develop the tumorigenic phenotype of Pten null mice.
Furthermore, to develop a novel therapeutic approach for melanoma, we studied the cytotoxic effects of an glycolysis inhibitor 3-bromopyruvate (3-BP) in both in vivo and in vitro mouse melanoma model. 3-BP induced cell death in melanoma cells and increased intracellular reactive oxygen species.Interestingly, 3-BP also induced cell death in colony forming cells and slow cycling cells. Taken together, these findings provided the evidences that 3-BP is a promising anticancer drug.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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