High level functional expression of the ABCG2 multidrug transporter in undifferentiated human embryonic stem cells.
Expression of multidrug resistance ABC transporters has been suggested as a functional marker and chemoprotective element in early human progenitor cell types. In this study we examined the expression and function of the key multidrug-ABC transporters, ABCB1, ABCC1 and ABCG2 in two human embryonic stem (HuES) cell lines. We detected a high level ABCG2 expression in the undifferentiated HuES cells, while the expression of this protein significantly decreased during early cell differentiation. ABCG2 in HuES cells provided protection against mitoxantrone toxicity, with a drug-stimulated overexpression of the transporter. No significant expression of ABCB1/ABCC1 was found either in the undifferentiated or partially differentiated HuES cells. Examination of the ABCG2 mRNA in HuES cells indicated the use of selected promoter sites and a truncated 3' untranslated region, suggesting a functionally distinct regulation of this transporter in undifferentiated stem cells. The selective expression of the ABCG2 multidrug transporter indicates that ABCG2 can be applied as a marker for undifferentiated HuES cells. Moreover, protection of embryonic stem cells against xenobiotics and endobiotics may depend on ABCG2 expression and regulation.
Apáti
Agota
A
Membrane Research Group of the Hungarian Academy of Sciences, Semmelweis University and National Blood Center, 1113 Budapest, Diószegi u. 64, Hungary.
Orbán
Tamás I
TI
Varga
Nóra
N
Németh
Andrea
A
Schamberger
Anita
A
Krizsik
Virág
V
Erdélyi-Belle
Boglárka
B
Homolya
László
L
Várady
György
G
Padányi
Rita
R
Karászi
Eva
E
Kemna
Evelien W M
EW
Német
Katalin
K
Sarkadi
Balázs
B
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis; D002454:Cell Differentiation; D002478:Cells, Cultured; D018432:Drug Resistance, Multiple / Q000235:genetics; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D019085:Fluorescent Antibody Technique, Direct; D006801:Humans; D008942:Mitoxantrone / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D015415:Biomarkers; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D008942:Mitoxantrone