| Autor: |
Dolci ED; Department of Pharmacology, University of Vermont, College of Medicine, Burlington 05405., Abramson R, Xuan Y, Siegfried J, Yuenger KA, Yassa DS, Tritton TR |
| Jazyk: |
angličtina |
| Zdroj: |
International journal of cancer [Int J Cancer] 1993 May 08; Vol. 54 (2), pp. 302-8. |
| DOI: |
10.1002/ijc.2910540223 |
| Abstrakt: |
KB-A1 and KB-A10 are 2 multi-drug-resistant cell lines which are 100- and 1,000-fold resistant to Adriamycin, respectively. We have examined the expression of P-glycoprotein at the molecular and cellular levels in these human carcinoma cells. Both MDR cell lines, when compared to the parental KB-3-1, show characteristic increases in mdr 1 gene copy number, an increase in mdr 1 mRNA expression, a corresponding increase in transcription rate and a consequent over-expression of P-glycoprotein. However, the more highly resistant KB-A10 cells have a lower gene copy number, express less mdr 1 mRNA and contain less P-glycoprotein than the A1 cell line. To determine whether higher levels of cellular resistance were attributable to enhanced efficacy of P-glycoprotein or to other cellular regulatory mechanisms, we examined other major cellular properties known to be associated with the mdr phenotype. Both the KB-A1 and KB-A10 lines exhibit similar increases in protein kinase C activity as compared to the drug-sensitive parent. In addition, neither glutathione-S-transferase nor topoisomerase II activities account for enhanced resistance of the KB-A10 cells. The above observations are contrary to the premise that the level of drug resistance is necessarily proportional to expression of P-glycoprotein or to other common factors thought to participate in drug insensitivity; consequently, new mechanisms of resistance must be in operation in these cells. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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