Cell cycle arrest and astrocytic differentiation resulting from PTEN expression in glioma cells
| Autor: | Jun-ichi Adachi, Katsumi Ohbayashi, Tomio Sasaki, Tomonari Suzuki |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Tumor suppressor gene
Cellular differentiation medicine.disease_cause Glioma Glial Fibrillary Acidic Protein Tumor Cells Cultured medicine Humans PTEN Genes Tumor Suppressor Regulation of gene expression Extracellular Matrix Proteins biology Tumor Suppressor Proteins Cell Cycle G1 Phase PTEN Phosphohydrolase Cell Differentiation Transfection Cell cycle medicine.disease Phosphoric Monoester Hydrolases Gene Expression Regulation Neoplastic Astrocytes biology.protein Cancer research Carcinogenesis Cell Division Plasmids |
| Zdroj: | Journal of Neurosurgery. 91:822-830 |
| ISSN: | 0022-3085 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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