Apáti Agota, Orbán Tamás I, Varga Nóra, Németh Andrea, Schamberger Anita, Krizsik Virág, Erdélyi-Belle Boglárka, Homolya László, Várady György, Padányi Rita, Karászi Eva, Kemna Evelien W M, Német Katalin, Sarkadi Balázs
Membrane Research Group of the Hungarian Academy of Sciences, Semmelweis University and National Blood Center, 1113 Budapest, Diószegi u. 64, Hungary.
Biochim Biophys Acta. 2008 Dec;1778(12):2700-9. doi: 10.1016/j.bbamem.2008.08.010. Epub 2008 Aug 20.
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.
多药耐药ABC转运蛋白的表达已被认为是早期人类祖细胞类型中的一种功能标志物和化学保护元件。在本研究中，我们检测了两种人类胚胎干细胞（HuES）系中关键多药ABC转运蛋白ABCB1、ABCC1和ABCG2的表达及功能。我们在未分化的HuES细胞中检测到高水平的ABCG2表达，而在细胞早期分化过程中该蛋白的表达显著降低。HuES细胞中的ABCG2对米托蒽醌毒性具有保护作用，且转运蛋白受药物刺激而过度表达。在未分化或部分分化的HuES细胞中均未发现ABCB1/ABCC1的显著表达。对HuES细胞中ABCG2 mRNA的检测表明，其使用了特定的启动子位点和截短的3'非翻译区，提示该转运蛋白在未分化干细胞中存在功能上不同的调控。ABCG2多药转运蛋白的选择性表达表明，ABCG2可作为未分化HuES细胞的标志物。此外，胚胎干细胞对外源生物和内源生物的保护作用可能取决于ABCG2的表达和调控。
