High level functional expression of the ABCG2 multidrug transporter in undifferentiated human embryonic stem cells

Membrane Research Group of the Hungarian Academy of Sciences, Semmelweis University and National Blood Center, 1113 Budapest, Diószegi u. 64, Hungary
Biochimica et Biophysica Acta (Impact Factor: 4.66). 12/2008; 1778(12):2700-2709. DOI: 10.1016/j.bbamem.2008.08.010
Source: PubMed


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.

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Available from: Tamás I Orbán, Oct 05, 2015
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    • "First, what is the role of repressed expression of Cell Reports 6, 1165–1174, March 27, 2014 ª2014 The Authors 1169 ABCB1 and ABCG2 in pluripotent cells? Mixed results have previously been reported about the expression of ABCG2 in ESCs: Zeng et al. observed low expression levels of ABCG2 in human, but not mouse, ESCs (Zeng et al., 2009), and others detected high-level expression of ABCG2 in hESCs (Apá ti et al., 2008). Our results support the model in which expression of ABCB1 and ABCG2 is repressed in hESCs and iPSCs. "
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    ABSTRACT: A small-molecule fluorescent probe specific for human pluripotent stem cells would serve as a useful tool for basic cell biology research and stem cell therapy. Screening of fluorescent chemical libraries with human induced pluripotent stem cells (iPSCs) and subsequent evaluation of hit molecules identified a fluorescent compound (Kyoto probe 1 [KP-1]) that selectively labels human pluripotent stem cells. Our analyses indicated that the selectivity results primarily from a distinct expression pattern of ABC transporters in human pluripotent stem cells and from the transporter selectivity of KP-1. Expression of ABCB1 (MDR1) and ABCG2 (BCRP), both of which cause the efflux of KP-1, is repressed in human pluripotent stem cells. Although KP-1, like other pluripotent markers, is not absolutely specific for pluripotent stem cells, the identified chemical probe may be used in conjunction with other reagents.
    Cell Reports 03/2014; 6(6). DOI:10.1016/j.celrep.2014.02.006 · 8.36 Impact Factor
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    • "It has been reported that 3′UTR shortening of oncogene mRNAs in cancer cells leads to increased protein abundance [54,56]. Intriguingly, the truncation of the ABCG2 3′UTR has also been reported in an undifferentiated human embryonic stem (HuES) cell line where its high ABCG2 expression was associated with the short 3′UTR variant forms [57]. In contrast, another differentiated HuES cell line with lower ABCG2 levels possesses a longer 3′UTR variant [57]. "
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    ABSTRACT: Multidrug resistance (MDR) is a major obstacle to successful cancer treatment. It is often associated with an increased efflux of a variety of structurally unrelated anticancer drugs by ATP-binding cassette (ABC) transporters including P-gp, ABCG2 and MRP1. MicroRNAs (miRNAs) are small non-coding RNAs that govern posttranscriptional regulation of target genes by interacting with specific sequences in their 3[prime] untranslated region (3[prime]UTR), thereby promoting mRNA degradation or suppressing translation. Accumulating evidence suggests that alterations in miRNAs contribute to resistance to anticancer drugs. While miRNAs are well-known to be dysregulated in cancer, recent literature revealed that miRNA levels in biological samples may be correlated with chemotherapy response. This review summarized the coordinated network by which miRNA regulated MDR transporters. The usefulness of miRNAs as prognostic biomarkers for predicting chemotherapeutic outcome is discussed. MiRNAs may also represent druggable targets for circumvention of MDR.
    Journal of Biomedical Science 12/2013; 20(1):99. DOI:10.1186/1423-0127-20-99 · 2.76 Impact Factor
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    • "In contrast, the expression of both genes was inversely expressed in CD90- cells suggesting a complimentary effect of both genes in overcoming the toxicity of DOX. The relation of ABCG2 with progenitor cells and differentiation had been reported in undifferentiated human embryonic cells [31] and hematopoietic system [32]. Accordingly, the functional activity of this transporter to target CD90 cells in drug therapy must be considered. "
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    ABSTRACT: Although the CD90 (Thy-1) was proposed as biomarker of several tumors and cancer stem cells, the involvement of this molecule in the progression of hepatocellular carcinoma (HCC) and other less frequent hepatic neoplasms is still undefined. The distribution of CD90 was investigated both in in vivo (human tissues samples) and in vitro (human HCC cell line JHH-6). A total of 67 liver tumors were analyzed: 51 HCC, 6 cholangiocarcinoma and 10 hepatoblastoma. In all cases, paired tissue sample of both the tumor and cirrhotic liver was available. Hepatic tissue obtained in 12 healthy livers was used as control. CD90 gene expression was studied by RT-qPCR, protein expression was assessed by quantitative Western Blot, immunofluorescence and flow cytometry. The CD90 expression analysis showed a significant increment in tumor compared to both its paired cirrhotic tissue and normal liver (p<0.05 and p<0.001, respectively). This increase was accompanied by the up-regulation of stromal component in the cancer, as demonstrated by alpha smooth muscle actin staining. In vitro analysis of JHH-6 cell line showed a higher proliferation capacity of CD90(+) compared to CD90(-) cells (p<0.001), also noticed in 3D clonogenic assay (p<0.05), associated by a significant higher expression of the promoting factors (hepatocyte growth factor, fibroblast associated protein and alpha smooth muscle actin 2). A higher expression of the breast cancer resistance protein was found in CD90(+) subpopulation while the multidrug resistance protein 1 showed an opposite behavior. Collectively, these results point to the importance of CD90 in the HCC.
    PLoS ONE 10/2013; 8(10):e76830. DOI:10.1371/journal.pone.0076830 · 3.23 Impact Factor
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