Altered nuclear localization of bax protein in BCNU-resistant glioma cells
| Autor: | A, Joy, S, Panicker, J R, Shapiro |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Time Factors
Blotting Western Green Fluorescent Proteins bcl-X Protein Fluorescent Antibody Technique Gene Expression Apoptosis Transfection Membrane Potentials Proto-Oncogene Proteins Nucleolus Organizer Region Tumor Cells Cultured Humans Annexin A5 Antineoplastic Agents Alkylating bcl-2-Associated X Protein Brain Neoplasms Proteins Glioma Carmustine Mitochondria Neoplasm Proteins Luminescent Proteins Microscopy Fluorescence Proto-Oncogene Proteins c-bcl-2 Drug Resistance Neoplasm Cell Nucleolus |
| Zdroj: | Journal of neuro-oncology. 49(2) |
| ISSN: | 0167-594X |
| Popis: | To investigate the role of apoptosis suppression in glioma chemotherapy resistance, protein levels and subcellular localization of bcl-2 family members were investigated in 2 pairs of sensitive cell lines and their in vitro generated resistant derivatives. The alkylating agent, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), induced apoptosis in both sensitive cell strains and apoptosis was suppressed in both resistant derivatives. Both resistant cell lines contained altered regulation of a bcl-2 related protein consistent with the suppression of apoptosis. Independent of which bcl-2 family member was dysregulated, resistance was associated with altered regulation in the subcellular localization of bax protein. Following BCNU treatment, bax accumulated in nucleoli and a nuclei containing fraction of sensitive cells but not their resistant derivatives. Nuclear accumulation was an early event in apoptosis induction. These data indicates altered subcellular localization of bax may play a role in resistance. In addition, the association between an early, nucleolar localization of bax and the induction of apoptosis suggests that localization of bax to nucleoli may play a role in apoptosis-induction of glioma cells. |
| Databáze: | OpenAIRE |
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