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2006 Fiscal Year Final Research Report Summary

Radiosensitization of hypoxic cancer cells by activation of mTOR signaling

Research Project

Project/Area Number 17591314
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Radiation science
Research InstitutionOsaka Medical Center for Cancer and Cardiovascular Diseases Osaka Prefectural Hospital Organization

Principal Investigator

MUKAI Mutsuko  Osaka Medical Center for Cancer and Cardiovascular Diseases Osaka Prefectural Hospital Organization, Biochemistry, Principal investigator, 研究所, 主任研究員 (20342991)

Co-Investigator(Kenkyū-buntansha) INOUE Masahiro  Osaka Medical Center for Cancer and Cardiovascular Diseases Osaka Prefectural Hospital Organization, Biochemistry, director, 研究所, 総括研究員 (10342990)
Project Period (FY) 2005 – 2006
Keywordshypoxia / mTOR / PI3K / apoptosis / radiosensitization
Research Abstract

mTOR (mammalian target of rapamycin) is activated and contributes to proliferation and survival of cancer cells under oxygenated and nutritionally rich conditions. On the other hand, under hypoxic and nutritionally poor conditions, mTOR signal is suppressed, although the physiological role of the suppression had not been clarified. This study aimed at elucidating the correlation between mTOR signaling and radiosensitivity under hypoxic conditions.
We examined a human cancer cell line, AsPC-1, which was hypoxia resistant. IGF treatment increased mTOR activity and radiosensitivity in parallel under hypoxic conditions. Inhibition of PI3K or mTOR activity by LY294002 or rapamycin decreased radiosensitivity. These results suggest that mTOR signaling affects radiosensitivity in opposite way under normoxia and hypoxia. We also found that IGF stimulation generate endoplasmic reticulum stress under hypoxic conditions, and that CHOP played critical role in cell death (Cancer Research, in revision). CHOP was necessary for the induction of apoptosis by IGF treatment under hypoxic conditions.
We also tried TAT-ODD system equipped with active form of Rheb. AsPC-1 cells treated with TAT-ODD-rheb could not stimulate mTOR signaling under hypoxic conditions. In AsPC-1 cells, other factors in addition to rheb are necessary to activate mTOR signaling under hypoxic conditions. Radiosensitization by activating mTOR signaling under hypoxic area in vivo remains to be elucidated.

  • Research Products

    (3 results)

All 2006 2005

All Journal Article (3 results)

  • [Journal Article] RhoC is essential for TGF-beta1-induced invasive capacity of rat ascites hepatoma cells2006

    • Author(s)
      Mukai M., Endo H., Iwasaki T., et al.
    • Journal Title

      Biochem Biophys Res Commun 346・1

      Pages: 74-82

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] RhoC is essential for TGF-beta1-induced invasive capacity of rat ascites hepatoma cells2006

    • Author(s)
      Mukai M., Endo H., Iwasaki T., et al.
    • Journal Title

      Biochem Biophys Res Commun 346.1

      Pages: 74-82

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Cross talk between apoptosis and invasion signaling in cancer cells through caspase-3 activation.2005

    • Author(s)
      Mukai M, Kusama T, Hamanaka Y, et al.
    • Journal Title

      Cancer Res 65

      Pages: 9121-9125

    • Description
      「研究成果報告書概要(和文)」より

URL: 

Published: 2008-05-27  

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