Physiological Functions of Pten in Mouse Tissues.

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  • Kishimoto Hiroyuki
    Department of Biochemistry, Akita University School of Medicine
  • Hamada Koichi
    Department of Biochemistry, Akita University School of Medicine
  • Saunders Mary
    Advanced Medical Discovery Institute and Department of Medical Biophysics, University of Toronto
  • Backman Stephanie
    Advanced Medical Discovery Institute and Department of Medical Biophysics, University of Toronto
  • Sasaki Takehiko
    Department of Pharmacology, Tokyo Metropolitan Institute of Medical Science and PRESTO, Japan Science and Technology Corporation (JST)
  • Nakano Toru
    Department of Molecular Cell Biology, Research Institute for Microbial Disease, Osaka University
  • Mak Tak Wah
    Advanced Medical Discovery Institute and Department of Medical Biophysics, University of Toronto
  • Suzuki Akira
    Department of Biochemistry, Akita University School of Medicine

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Description

PTEN is a tumor suppressor gene mutated in many human sporadic cancers and in hereditary cancer syndromes such as Cowden disease, Bannayan-Zonana syndrome and Lhermitte-Duclos disease. The major substrate of PTEN is PIP3, a second messenger molecule produced following PI3K activation induced by variety of stimuli. PIP3 activates the serine-threonine kinase PKB/Akt which is involved in anti-apoptosis, proliferation and oncogenesis. In mice, heterozygosity for a null mutation of Pten (Pten+/- mice) frequently leads to the development of a variety of cancers and autoimmune disease. Homozygosity for the null mutation (Pten -/- mice) results in early embryonic lethality, precluding the functional analysis of Pten in various organs. To investigate the physiological functions of Pten in viable mice, various tissue-specific Pten mutations have been generated using the Cre-loxP system. This review will summarize the phenotypes of conditional mutant mice lacking Pten function in specific tissues, and discuss how these phenotypes relate to the physiological roles of Pten in various organ systems.<br>

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