Effect of Ionizing Radiation on AP-1 Binding Activity and Basic Fibroblast Growth Factor Gene Expression in Drug-sensitive Human Breast Carcinoma MCF-7 and Multidrug-resistant MCF-7/ADR Cells
| Autor: | Peter M. Corry, Geza Erdos, Christine M. Berns, Yong J. Lee, Sandra Galoforo, Anjali K. Gupta, D. K. Ways |
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| Rok vydání: | 1995 |
| Předmět: |
Cell Survival
Molecular Sequence Data Basic fibroblast growth factor Breast Neoplasms Biology Biochemistry Piperazines chemistry.chemical_compound Genes jun 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine Radiation Ionizing Gene expression Tumor Cells Cultured Humans Northern blot Enzyme Inhibitors skin and connective tissue diseases Molecular Biology Transcription factor Protein Kinase C Protein kinase C Base Sequence Genes fos Cell Biology Transfection Isoquinolines Molecular biology Drug Resistance Multiple Gene Expression Regulation Neoplastic Transcription Factor AP-1 Oligodeoxyribonucleotides chemistry MCF-7 Drug Resistance Neoplasm Cell culture Cancer research Fibroblast Growth Factor 2 Protein Binding |
| Zdroj: | Journal of Biological Chemistry. 270:28790-28796 |
| ISSN: | 0021-9258 |
| Popis: | We studied the effect of ionizing radiation on the activation of the AP-1 transcription factors and the regulation of basic fibroblast growth factor (bFGF) gene expression in drug-sensitive human breast carcinoma (MCF-7) cells and its drug-resistant variant (MCF-7/ADR) cells. Northern blot and gel mobility shift assays showed that 135 cGy of ionizing radiation induced c-jun and c-fos gene expression, AP-1 binding activity, as well as bFGF gene expression in MCF-7/ADR cells. In MCF-7 cells, however, we observed little/no induction of bFGF gene expression and AP-1 binding activity after the stress. Nevertheless, MCF-7 cells transfected with plasmids containing c-jun gene contain high levels of bFGF protein. H-7 (60 micrograms/ml), a potent protein kinase C (PKC) inhibitor, inhibited the stress-induced AP-1 binding activity and bFGF gene expression in MCF-7/ADR cells. Corroborating this observation, overexpression of PKC alpha induced bFGF gene expression in MCF-7 cells. Taken together, these results suggest that stress-induced bFGF gene expression is mediated through the activation of PKC and AP-1 transcription factors. Differences in the levels of PKC activity and AP-1 binding factors may be responsible for differential expression of bFGF among breast cancer cell lines. Although there are large differences in response to ionizing radiation between MCF-7 and MCF-7/ADR cell lines, we observed no significant differences in radiocytotoxicity between them. |
| Databáze: | OpenAIRE |
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