Enhanced exposure of phosphatidylserine in human gastric carcinoma cells overexpressing the half-size ABC transporter BCRP (ABCG2)

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Abstract
Members of the ABC (ATP-binding cassette) transporter super-family are emerging to be involved in lipid transport. In the present study, we studied the organization of phospholipids in the plasma membrane of EPG85-257 human gastric carcinoma cells overexpressing BCRP (breast cancer resistance protein, ABCG-2), a half-size transporter belonging to the ABCG subfamily. A significantly increased plasma membrane association of the PS (phosphatidylserine)-binding probe FITC–Annexin V in comparison with control cells was observed. Treatment of BCRP-overexpressing cells with the inhibitor Tryprostatin A decreased FITC–Annexin V binding almost to the control level. This suggests an enhanced exposure of PS in BCRP-overexpressing cells, which is dependent on functional BCRP. A role of BCRP in the transverse distribution of lipids in the plasma membrane is supported by the increased outward transport of the lipid analogue C6-N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-PS in BCRP-overexpressing EPG85-257 cells and MCF-7 human breast cancer cells. As shown for BCRP-overexpressing EPG85-257 cells, enhanced outward redistribution of the lipid analogue is inhibited by Tryprostatin A as well as by reduction of BCRP expression on transfection with an anti-BCRP-ribozyme. We also observed an enhanced outward transport of C6-N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-phosphatidylcholine in BCRP-overexpressing EPG85-257 cells, suggesting that the influence of BCRP on transverse lipid organization is not highly specific.

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