Topology and Function of Human P-Glycoprotein in Multidrug Resistant Breast Cancer Cells.
Abstract
Overexpression of P-glycoprotein (Pgp), 170-kDa glycoprotein coded by the MDR1 gene in humans, confers multidrug resistance in various tumors. Pgp actively pumps various substrates including chemotherapeutic agents out of cells and is associated with swelling-activated chloride currents (Icls). Our aim is to determine the relationship between Pgp structure and function. We determined regulatory elements involved in C-half topogenesis. Our results indicate that C-half topogenesis is: (1) independent of N-half sequence, (2) independent of expression system, and (3) partially regulated by charged amino acids surrounding transmembrane segments. To investigate the relationship between Pgp and Icls, we plan on characterizing the channel(s) underlying Icls in isolated rat hepatocytes and blood cells. Using the whole-cell patch clamp technique, we examined several properties of Icls in rat hepatocytes and observed: (1) outwardly-rectifying currents, (2) minimal current inactivation at positive voltages, (3) Icls activation without pipette ATP, (4) block of with NPPB or DIDS, and (5) selectivity sequence of SCN->I-congruent to NO3-congruent to Br-> Cl-> gluconate. Our aim is to study the same properties in isolated rat blood cells to establish whether or not the channel accounting for Icls the same.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1995
- Accession Number
- ADB218909
Entities
People
- Ernest S. Han
- Luis Reuss
Organizations
- University of Texas Medical Branch