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[Atypical MDR]
A Yokomizo1, K Taniguchi, S Hasegawa
1Dept. of Biochemistry, School of Medicine, Kyusyu University, Fukuoka, Japan.
Abstract:
Multiple drug resistance(MDR) is a major clinical obstacle in cancer chemotherapy. Acquirement of MDR phenotype in cancer cells is often associated with enhanced expression of human MDR-1 gene: MDR-1 gene codes membranous P-glycoprotein which catalyses energy-dependent outward transport of anticancer agents. By contrast, MDR cancer cell lines without overexpression of P-glycoprotein are called as atypical MDR (at MDR) cells. The acquirement of at MDR has been shown to be partly associated with altered DNA topoisomerase II. Furthermore, a new ATP binding cassette (ABC) family, MRP gene has just recently shown to involve in acquirement of at-MDR in cancer cell lines, which do not express both altered topoisomerase II and P-glycoprotein.
Insights
Multiple drug resistance (MDR) hinders cancer chemotherapy. Atypical MDR involves altered DNA topoisomerase II and the MRP gene, independent of P-glycoprotein.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Multiple drug resistance (MDR) is a significant challenge in cancer treatment.
- The MDR-1 gene encodes P-glycoprotein, a transporter protein often overexpressed in MDR cancer cells.
- Atypical MDR (atMDR) occurs in cells lacking P-glycoprotein overexpression.
Purpose of the Study:
- To investigate the mechanisms underlying atypical MDR.
- To explore the role of DNA topoisomerase II and the MRP gene in atMDR development.
Main Methods:
- Analysis of MDR cancer cell lines.
- Assessment of P-glycoprotein expression.
- Evaluation of DNA topoisomerase II activity.
- Investigation of the ATP binding cassette (ABC) transporter superfamily, including the MRP gene.
Main Results:
- atMDR can arise independently of P-glycoprotein.
- Altered DNA topoisomerase II is implicated in some cases of atMDR.
- The MRP gene, a member of the ABC transporter family, is newly identified as involved in atMDR in cells lacking P-glycoprotein and altered topoisomerase II.
Conclusions:
- Atypical MDR involves complex mechanisms beyond P-glycoprotein.
- The MRP gene represents a novel target for overcoming atMDR in specific cancer contexts.