Molecular Study of Interactions between P-Glycoprotein and Anticancer Drugs.
Annual rept. 1 Aug 94-31 Jul 95,
TEXAS UNIV MEDICAL BRANCH AT GALVESTON
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P-glycoprotein is a plasma membrane protein that functions as a drug transporter and is responsible for multidrug resistance in some breast cancers. In the past one year, we have generated two site-specific antibodies and used them to determine the topologies of P-glycoprotein in multidrug resistant cancer cells. We found that P-glycoproteins in the plasma membrane of mammalian cells express at least two alternate topologies. This observation is consistent with our previous study using cell-free expression system. The more than one topology feature of P-glycoprotein may be responsible for its multifunctional nature. We have also been able to express the transmembrane domains of P-glycoprotein in bacteria. The success in this study will allow us to map the drug-binding domain in P-glycoprotein and study the drng-P-glycoprotein interactions.
- Medicine and Medical Research