Inhibition of N-linked Glycosylation of P-glycoprotein by Tunicamycin Results in a Reduced Multidrug Resistance Phenotype

Overview

Journal Br J Cancer

Specialty Oncology

Date 1995 Apr 1

PMID 7710927

Citations 16

Authors

R Kramer

T K Weber

R Arceci

N Ramchurren

W V Kastrinakis

G Steele Jr

I C Summerhayes

Affiliations

Soon will be listed here.

Abstract

Characterisation of altered glycosylation of P-glycoprotein (P-gp) found associated with the absence of a multidrug resistance (MDR) phenotype in cell lines prompted an investigation to assess the role of post-translational processing in establishing P-gp efflux pump functionally. The clone A cell line used in this study displays a strong MDR phenotype mediated by high constitutive levels of expression of P-gp. Incubation of clone A cells with tunicamycin for different periods resulted in a time-dependent increase in daunorubicin accumulation, reflecting a reduction in P-gp function. Parallel experiments conducted with verapamil resulted in no loss of P-gp functionality in clone A cells. Reduction in surface-associated P-gp following exposure to tunicamycin was established by FACS analysis, Western blot analysis and immunoprecipitation of surface-iodinated P-gp. In addition, immunoprecipitation of P-gp from 32P-orthophosphate-labelled cells demonstrated reduced phosphorylation of P-gp associated with tunicamycin exposure. From these studies we conclude that glycosylation of P-gp is required to establish the cellular MDR phenotype.

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