Differential expression of DNA topoisomerase II alpha and -beta in P-gp and MRP-negative VM26, mAMSA and mitoxantrone-resistant sublines of the human SCLC cell line GLC(4)
| Autor: | Withoff, S., Devries, Ege, Nicol Keith, Nienhuis, Ef, Vandergraaf, Wta, Uges, Dra, Mulder, Nh |
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| Přispěvatelé: | Faculteit Medische Wetenschappen/UMCG, Groningen Research Institute of Pharmacy, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Molecular Neuroscience and Ageing Research (MOLAR) |
| Jazyk: | angličtina |
| Rok vydání: | 1996 |
| Předmět: |
DRUG-RESISTANCE
GLC(4) NIH-3T3 CELLS macromolecular substances PROTEIN MRP FORMS chemotherapy GENE topoisomerase II alpha CYTO-TOXICITY carbohydrates (lipids) multidrug resistance ACID SUBCELLULAR-DISTRIBUTION topoisomerase II beta BREAST-CANCER lipids (amino acids peptides and proteins) MESSENGER-RNA |
| Zdroj: | British Jounal of Cancer, 74(12), 1869-1876. Nature Publishing Group ResearcherID |
| ISSN: | 0007-0920 |
| Popis: | Sublines of the human small-cell lung carcinoma (SCLC) cell line GLC(4) with acquired resistance to teniposide, amsacrine and mitoxantrone (GLC(4)/VM(20x), GLC(4)/AM(3x) and GLC(4)/MIT(60x), respectively) were derived to study the contribution of DNA topoisomerase II alpha and -beta (TopuII alpha and -beta) to resistance for TopoII-targeting drugs. The cell lines did not overexpress P-glycoprotein or the multidrug resistance-associated protein but were cross-resistant to other TopoII drugs. GLC(4)/VM(20x) showed a major decrease in TopoII alpha protein (54%; for all assays presented in this paper the GLC(4) level was defined to be 100%) without reduction in TopoII beta protein; GLC(4)/AM(3x) showed only a major decrease in TopoII beta protein (to 18%) and not in TopoII alpha. In GLC(4)/MIT(60x), the TopoII alpha and -beta protein levels were both decreased (TopoII alpha to 31%:TopoII beta protein was undetectable). The decrease in TopoII alpha protein in GLC(4)/VM(20x) and GLC(4)/MIT(60x), was mediated by decreased TopoII alpha mRNA levels. Loss of TopoII alpha gene copies contributed to the mRNA decrease in these cell lines. Only in the GLC(4)/MIT(60x) cell line was an accumulation defect observed for the drug against which the cell line was made resistant. In conclusion, TopoII alpha and -beta levels were decreased differentially in the resistant cell lines, suggesting that resistance to these drugs may be mediated by a decrease in a specific isozyme. |
| Databáze: | OpenAIRE |
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