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Expression, Detergent Solubilization, and Purification of a Membrane Transporter, the MexB Multidrug Resistance Protein
Published on: December 3, 2010
Golgi complex is brefeldin A resistant in multidrug resistant cells
M V Erokhina1, A A Stavrovskaya, G E Onishchenko
1Institute of Carcinogenesis, Blokhin Cancer Research Center, Russian Academy of Medical Sciences, Moscow. rak@sunny.aha.ru
Summary
Multidrug resistance (MDR) in cancer involves P-glycoprotein (Pgp). Brefeldin A (BFA) reveals distinct vacuolar system responses in Pgp-expressing cells, impacting cancer chemotherapy effectiveness.
Area of Science:
- Cell Biology
- Molecular Biology
- Cancer Research
Background:
- Multidrug resistance (MDR) is a major cause of chemotherapy failure in cancer.
- Overexpression of P-glycoprotein (Pgp) confers MDR by enabling resistant tumor cells.
- Previous work showed Pgp-mediated MDR involves cytoskeleton and vacuolar system reorganization.
Purpose of the Study:
- To investigate vacuolar system properties in Pgp-expressing cells.
- To understand the effects of Brefeldin A (BFA) on parental and resistant cells.
- To explore the role of BFA targets in the evolution of MDR.
Main Methods:
- Utilized Syrian hamster embryo fibroblasts transformed by Raus sarcoma virus.
- Compared the effects of Brefeldin A (BFA) on parental and Pgp-expressing resistant sublines.
- Assessed BFA's impact on Golgi apparatus structure and vesicular transport.
Main Results:
- Brefeldin A (BFA) differentially affects parental and resistant cells.
- In parental cells, BFA impacts both Golgi apparatus structure and vesicular transport.
- In resistant cells, BFA affects vesicular transport but not Golgi apparatus structure.
Conclusions:
- Vacuolar system responses to BFA differ between parental and Pgp-expressing cells.
- These differences suggest distinct BFA targets contributing to MDR evolution.
- Understanding these mechanisms may offer new avenues for overcoming chemotherapy resistance.
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