Suppression of putative tumour suppressor gene GLTSCR2 expression in human glioblastomas.
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.
Kim
Y-J
YJ
Department of Pathology and Medical Research Centre for Bioreaction to Reactive Oxygen Species, School of Medicine, Kyung Hee University, Seoul 130-701, Korea.
Cho
Y-E
YE
Kim
Y-W
YW
Kim
J-Y
JY
Lee
S
S
Park
J-H
JH
D000328:Adult; D001254:Astrocytoma / Q000235:genetics / Q000473:pathology; D001932:Brain Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D016009:Chi-Square Distribution; D005260:Female; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000235:genetics*
C500712:NOP53 protein, human; D025521:Tumor Suppressor Proteins