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• W1972620541 endingPage "1604" @default.
• W1972620541 startingPage "1597" @default.
• W1972620541 abstract "Many multidrug-resistam (MDR) cell lines overexpress the epidermal growth factor receptor (EGFR) as well as P-glycoprotein (P-gp). However, the role of the increased EGFR in P-gp-mediated drug resistance remains unclear. Since recent studies suggest that activation of phospholipase C (PLC) could increase the phosphorylation of P-gp, and activation of the EGFR would also activate PLC, we investigated whether the effect of epidermal growth factor (EGF) on the phosphorylation of P-gp was mediated through PLC. Treatment of the human MDR hreast cancer cell line, MCF-7/AdrR, with EGF increased the phosphorylation of P-gp by 20–50%. The increased phosphorylation of P-gp was accompanied by stimulation of PLC activity, as measured by the production of inositol, 1,4,5-trisphosphate and diacylglycerol, products of phosphatidylinositol-4,5-bisphosphate hydrolysis. Treatment of MDR cells with EGF also had detectable effects on P-gp function. For example, following incubation of MCF-7/AdrR cells with EGF, we observed a consistent decrease in total vinblastine (VBL) accumulation. Kinetic analysis revealed this change to be due to an increase in membrane efflux. The latter was measured by the initial uptake velocity, which was inhibited by EGF. VBL uptake measured at 0–320 sec was inhibited by 20–40%, which was associated with a similar increase in VBL efflux. EGF had no effect on drug accumulation, uptake, or efflux in sensitive MCF-7 cells. These data indicate that EGF can modulate the phosphorylation and function of P-gp, and suggest that this effect may be initiated by the activation of PLC." @default.
• W1972620541 created "2016-06-24" @default.
• W1972620541 creator A5045432217 @default.
• W1972620541 creator A5054504492 @default.
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• W1972620541 date "1997-06-01" @default.
• W1972620541 modified "2023-10-18" @default.
• W1972620541 title "Regulation of the function of P-glycoprotein by epidermal growth factor through phospholipase C" @default.
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• W1972620541 doi "https://doi.org/10.1016/s0006-2952(97)82451-3" @default.
• W1972620541 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/9264311" @default.
• W1972620541 hasPublicationYear "1997" @default.
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