The xenobiotic transporter ABCG2 plays a novel role in differentiation of trophoblast-like BeWo cells.
Trophoblast cells undergo loss of plasma membrane lipid asymmetry during cell fusion without further progression to terminal phases of apoptosis. The nature of the anti-apoptotic mechanisms providing cell survival during this process is unknown. Using a BeWo cell model, we explored the role of the xenobiotic/lipid transporter ABCG2 in promoting cell survival during forskolin-induced differentiation. Suppression of ABCG2 expression by siRNA led to a marked increase in phosphatidylserine externalisation followed by accumulation of ceramides and increased apoptosis. Expression of markers of syncytial formation (beta-hCG and HERV-W) was decreased by ABCG2 silencing, although fusion was unaffected. These findings suggest that ABCG2 protects cells during the period of transient membrane instability associated with cell differentiation and fusion, highlighting a novel, previously unrecognised role of ABCG2 as a survival factor during the formation of the placental syncytium.
Evseenko
D A
DA
Liggins Institute, University of Auckland, Private Bag 92019, Auckland 1003, New Zealand. d.evseenko@auckland.ac.nz
Paxton
J W
JW
Keelan
J A
JA
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D017209:Apoptosis / Q000235:genetics; D002454:Cell Differentiation; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D005260:Female; D015726:Giant Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D010718:Phosphatidylserines / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D014327:Trophoblasts / Q000166:cytology* / Q000378:metabolism; D015262:Xenobiotics / Q000378:metabolism
C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D009363:Neoplasm Proteins; D010718:Phosphatidylserines; D034741:RNA, Small Interfering; D015262:Xenobiotics; D005576:Colforsin