R. Kramer et al., INHIBITION OF N-LINKED GLYCOSYLATION OF P-GLYCOPROTEIN BY TUNICAMYCINRESULTS IN A REDUCED MULTIDRUG-RESISTANCE PHENOTYPE, British Journal of Cancer, 71(4), 1995, pp. 670-675
Characterisation of altered glycosylation of P-glycoprotein (P-gp) fou
nd associated with the absence of a multidrug resistance (MDR) phenoty
pe in cell lines prompted an investigation to assess the role of post-
translational processing in establishing P-gp efflux pump functionalit
y. The clone A cell line used in this study displays a strong MDR phen
otype mediated by high constitutive levels of expression of P-gp. Incu
bation of clone A cells with tunicamycin for different periods resulte
d in a time-dependent increase in daunorubicin accumulation, reflectin
g a reduction in P-gp function. Parallel experiments conducted with ve
rapamil resulted in no loss of P-gp functionality in clone A cells. Re
duction in surface-associated P-gp following exposure to tunicamycin w
as established by FAGS analysis, Western blot analysis and immunopreci
pitation of surface-iodinated P-gp. In addition, immunoprecipitation o
f P-gp from P-32-orthophosphate-labelled cells demonstrated reduced ph
osphorylation of P-gp associated with tunicamycin exposure. From these
studies we conclude that glycosylation of P-gp is required to establi
sh the cellular MDR phenotype.