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Suppression of putative tumour suppressor gene GLTSCR2 expression in human glioblastomas

Authors

  • Y-J Kim,

    1. Department of Pathology and Medical Research Centre for Bioreaction to Reactive Oxygen Species, School of Medicine, Kyung Hee University, Seoul 130-701, Korea
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  • Y-E Cho,

    1. Department of Pathology and Medical Research Centre for Bioreaction to Reactive Oxygen Species, School of Medicine, Kyung Hee University, Seoul 130-701, Korea
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  • Y-W Kim,

    1. Department of Pathology and Medical Research Centre for Bioreaction to Reactive Oxygen Species, School of Medicine, Kyung Hee University, Seoul 130-701, Korea
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  • J-Y Kim,

    1. Department of Pathology and Medical Research Centre for Bioreaction to Reactive Oxygen Species, School of Medicine, Kyung Hee University, Seoul 130-701, Korea
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  • S Lee,

    1. Department of Pathology and Medical Research Centre for Bioreaction to Reactive Oxygen Species, School of Medicine, Kyung Hee University, Seoul 130-701, Korea
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  • J-H Park

    Corresponding author
    1. Department of Pathology and Medical Research Centre for Bioreaction to Reactive Oxygen Species, School of Medicine, Kyung Hee University, Seoul 130-701, Korea
    • Department of Pathology, College of Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemoon-Koo, Seoul 130-701, Korea.
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  • No conflicts of interest were declared .

Abstract

Glioma tumour-suppressor candidate region gene 2 (GLTSCR2/PICT-1) is localized within the well-known 1.4 Mb tumour-suppressive region of chromosome 19q, which is frequently altered in various human tumours, including diffuse gliomas. Aside from its chromosomal localization, several lines of evidence, including PTEN-phosphorylating and cell-killing activities, suggests that GLTSCR2 participates in the suppression of tumour growth and development. However, little is known about the biological functions and molecular mechanisms of GLTSCR2 as a tumour suppressor gene. We investigated the pathological significance of GLTSCR2 expression in association with the development and progression of glioblastomas, the most common malignant brain tumour. We used real-time PCR and western blot analysis to examine the expression levels of GLTSCR2 mRNA and protein in glioblastomas, normal brain tissue and in non-glial tumour tissue of different origin, and found that GLTSCR2 expression is down-regulated in glioblastomas. In addition, direct sequencing analysis and fluorescence in situ hybridization clearly demonstrates the presence of genetic alterations, such as a nonsense mutation and deletion, in the GLTSCR2 gene in glioblastomas. Finally, our immunohistochemical study demonstrates that GLTSCR2 is sequentially down-regulated according to the histological malignant progression of the astrocytic glial tumour. Taken together, our results suggest that GLTSCR2 is involved in astrocytic glioma progression. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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