An acidic environment changes cyclin D1 localization and alters colony forming ability in gliomas
| Autor: | William Harley, Kayoko Nishi, Joachim B. Schnier, Fredric A Gorin |
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| Rok vydání: | 2007 |
| Předmět: |
Cancer Research
Cytoplasm Proteasome Endopeptidase Complex Cell Survival Intracellular pH Active Transport Cell Nucleus Down-Regulation Biology Article Cyclin D1 Cell Line Tumor medicine Humans Enzyme Inhibitors RNA Small Interfering neoplasms Tumor Stem Cell Assay Cyclin Cell Proliferation Cell Nucleus Cell growth Brain Neoplasms Glioma Cell cycle Hydrogen-Ion Concentration Molecular biology Cell biology nervous system diseases Neurology Oncology Proteasome Cell culture Proteasome inhibitor Neurology (clinical) Extracellular Space Acids Proteasome Inhibitors medicine.drug |
| Zdroj: | Journal of neuro-oncology. 89(1) |
| ISSN: | 0167-594X |
| Popis: | The human glioma cell lines, U87 and T98G, were evaluated for their ability to survive and form colonies in an acidic environment of pH(ext) 6.0. In contrast to U87, which showed an 80-90% survival rate, only 40% of T98G cells survived 6 days at pH(ext) 6.0 and lost their colony forming ability when returned to a normocidic environment. Although both U87 and T98G cells maintain an intracellular pH (pH(i)) of 7.0 at pH(ext) 6.0 and arrest mostly in G1 phase of the cell cycle, only T98G demonstrated a major loss of cyclin D1 that was prevented by the proteasome inhibitor MG132. Colony forming ability was restored by stably transfecting T98G cells with a cyclin D1-expressing plasmid. Both U87 and T98G cells demonstrated increased cytoplasmic localization of cyclin D1 during exposure at pH(ext) 6.0. Upon prolonged (24 h) incubation at pH(ext) 6.0, nuclear cyclin D1 was nearly absent in T98G in contrast to U87 cells. Thus, an acidic environment triggers cytoplasmic localization and proteasomal degradation of cyclin D1. |
| Databáze: | OpenAIRE |
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