Document Detail

Cell cycle arrest and astrocytic differentiation resulting from PTEN expression in glioma cells.
MedLine Citation:
PMID:  10541240     Owner:  NLM     Status:  MEDLINE    
OBJECT: Genetic alterations of the PTEN gene (also known as MMAC1 or TEP1) have frequently been identified in high-grade gliomas, indicating that inactivation of PTEN plays a crucial role in human glioma progression. The aim of this study was to assess the biological significance of PTEN inactivation in the development of glioma. METHODS: The authors introduced wild-type PTEN complementary DNA into four human glioma cell lines (T98G, U-251MG, U-87MG, and A172) containing endogenous aberrant PTEN alleles. The number of colonies transfected with the wild-type PTEN was reduced to 15 to 32% of those found after transfection of a control vector, suggesting growth suppression by the exogenous PTEN. To analyze phenotypic alterations produced by PTEN expression, T98G-derived clones with inducible PTEN expression were further established using a tetracycline-regulated inducible gene expression system. Induction of PTEN expression suppressed the in vitro growth of T98G cells with accumulation of G1 phase cells. Furthermore, when cells were cultured in the presence of the extracellular matrix (ECM), PTEN expression caused distinct morphological changes, with multiple and elongated cytoplasmic processes similar to those of normal astrocytes. The level of glial fibrillary acidic protein, an intermediate protein specifically expressed in differentiated astrocytes, was upregulated concomitantly. CONCLUSIONS: These findings strongly indicate that exogenous PTEN expression inhibits the proliferation of glioma cells by inducing G1 arrest and elicits astrocytic differentiation in the presence of the ECM. Inactivation of PTEN would play an important role in the enhancement of unregulated growth of undifferentiated glioma cells.
J Adachi; K Ohbayashi; T Suzuki; T Sasaki
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of neurosurgery     Volume:  91     ISSN:  0022-3085     ISO Abbreviation:  J. Neurosurg.     Publication Date:  1999 Nov 
Date Detail:
Created Date:  1999-11-04     Completed Date:  1999-11-04     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0253357     Medline TA:  J Neurosurg     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  822-30     Citation Subset:  AIM; IM    
Department of Neurosurgery, Gunma University School of Medicine, Maebashi, Japan.
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MeSH Terms
Astrocytes / chemistry,  cytology*
Cell Cycle / physiology*
Cell Differentiation / drug effects,  physiology
Cell Division / drug effects,  physiology
Extracellular Matrix Proteins / pharmacology
G1 Phase / physiology
Gene Expression Regulation, Neoplastic*
Genes, Tumor Suppressor / physiology
Glial Fibrillary Acidic Protein / analysis
PTEN Phosphohydrolase
Phosphoric Monoester Hydrolases / genetics*
Tumor Cells, Cultured / cytology,  physiology
Tumor Suppressor Proteins*
Reg. No./Substance:
0/Extracellular Matrix Proteins; 0/Glial Fibrillary Acidic Protein; 0/Tumor Suppressor Proteins; EC 3.1.3.-/Phosphoric Monoester Hydrolases; EC protein, human; EC Phosphohydrolase

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