INT130295

Context Info Confidence 0.75 First Reported 2005 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 21 Total Number 22 Disease Relevance 9.75 Pain Relevance 3.42

transport (Abcg2) ATPase activity (Abcg2) plasma membrane (Abcg2) nucleus (Abcg2)

Anatomy Link Frequency stem cells 4 liver 2 lens 2 hematopoietic stem cells 1 MCF-7 1 Abcg2 (Mus musculus)

Pain Link Frequency Relevance Heat dexamethasone 26 99.92 cINOD 22 99.12 methotrexate 140 98.96 imagery 10 95.92 Paracetamol 22 95.12 Calcium channel 5 89.76 tolerance 20 73.88 Glutamate 6 67.68 COX-2 inhibitor 52 64.08 Bioavailability 13 60.28

Disease Link Frequency Relevance Heat Cancer 591 100.00 Breast Cancer 145 100.00 Myeloid Leukemia 342 99.84 Solid Tumor 12 99.08 INFLAMMATION 52 99.00 Injury 10 98.16 Rheumatoid Arthritis 25 96.88 Death 54 96.28 Apoptosis 199 96.26 Glioblastoma 3 95.40

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The present study further characterizes the expression of multidrug resistance-associated proteins 1-4 (Mrp1-4), breast cancer resistance protein (Bcrp) and sodium-taurocholate co-transporting polypeptide (Ntcp) in mouse liver following administration of the hepatotoxicants acetaminophen (APAP) and carbon tetrachloride (CCl4).

Gene_expression (expression) of Bcrp in liver associated with paracetamol and breast cancer

1) Confidence 0.75 Published 2006 Journal Toxicol. Sci. Section Abstract Doc Link 16177239 Disease Relevance 0.36 Pain Relevance 0.34

Alternatively, upregulation of the efflux transporter ABCG2 protein expression has been associated with MTX resistance in cancer cells [45], but no associations with SNPs evaluated in FPGS and clinical effects of MTX have been observed [44].

Gene_expression (expression) of ABCG2 associated with cancer and methotrexate

2) Confidence 0.68 Published 2010 Journal Human Genomics and Proteomics : HGP Section Body Doc Link PMC2958653 Disease Relevance 0.34 Pain Relevance 0.27

This resistance is mediated by many mechanisms including over-expression of proteins involved in inhibition of apoptosis (i.e, Bcl-2), leading to insensitivity of tumor cells to apoptotic stimuli; an up-regulation of DNA repair; alteration of the target; up-regulation of detoxification enzymes (i.e., Glutathione S-transferases); and extrusion of chemotherapeutic drugs by overexpression of ATP-binding cassette family proteins, such as MRP (multidrug resistant-associated protein) BCRP (breast cancer resistance protein or mitoxantrone resistance protein) because these proteins regulate absorption, distribution, and excretion of various pharmacologic compounds [141].

Gene_expression (overexpression) of BCRP associated with cancer, breast cancer and apoptosis

3) Confidence 0.65 Published 2010 Journal International Journal of Cell Biology Section Body Doc Link PMC2841246 Disease Relevance 0.95 Pain Relevance 0.09

Real-time semiquantitative RT-PCR showed that lens epithelial SP cells express higher levels of ABCG2 than non-SP cells.

Gene_expression (express) of ABCG2 in lens

4) Confidence 0.63 Published 2010 Journal Molecular Vision Section Body Doc Link PMC2890558 Disease Relevance 0 Pain Relevance 0.04

In vitro studies have revealed that the cellular response to folate deprivation is associated with increased expression of FPGS and decreased expression of ABCG2 [35], suggesting that the adaptive cellular response to low folate involves increased polyglutamation to promote the retention of folate.

Gene_expression (expression) of ABCG2

5) Confidence 0.59 Published 2010 Journal Human Genomics and Proteomics : HGP Section Body Doc Link PMC2958653 Disease Relevance 0.13 Pain Relevance 0.36

One important feature of CSCs is their resistance to the cytotoxicity of varous chemotherapeutic agents because of their relatively high expression levels of multiple drug resistance transporters such as ABCB1 (MDR1/PGP, P-glycoprotein) and ABCG2 (MXR/BCRP) [38].

Gene_expression (expression) of MXR in CSCs

6) Confidence 0.58 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2860989 Disease Relevance 1.22 Pain Relevance 0

Protein expression of Bcrp was unchanged with treatment.

Gene_expression (expression) of Bcrp

7) Confidence 0.58 Published 2006 Journal Toxicol. Sci. Section Abstract Doc Link 16177239 Disease Relevance 0.30 Pain Relevance 0.47

Immunostaining of liver sections obtained 48 h after hepatotoxicant treatment confirmed expression patterns of a subset of transporters (Bcrp, Ntcp, Mrp3, and Mrp4).

Gene_expression (expression) of Bcrp in liver

8) Confidence 0.58 Published 2006 Journal Toxicol. Sci. Section Abstract Doc Link 16177239 Disease Relevance 0.20 Pain Relevance 0.44

One important feature of CSCs is their resistance to the cytotoxicity of varous chemotherapeutic agents because of their relatively high expression levels of multiple drug resistance transporters such as ABCB1 (MDR1/PGP, P-glycoprotein) and ABCG2 (MXR/BCRP) [38].

Gene_expression (expression) of ABCG2 in CSCs

9) Confidence 0.52 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2860989 Disease Relevance 1.22 Pain Relevance 0

This is the reason why BCRP mediated resistance to imatinib is attenuated by imatinib induced reduction of BCRP expression (Nakanishi et al 2006).

Gene_expression (expression) of BCRP

10) Confidence 0.51 Published 2008 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2503652 Disease Relevance 0.20 Pain Relevance 0.03

SP cells expressed approximately 4.5-fold higher mRNA levels of the stem cell marker ABCG2 compared to non-SP cells, which strongly suggested that mouse lens SP cells isolated by FACS are stem cells.

Gene_expression (expressed) of ABCG2 in lens

11) Confidence 0.49 Published 2010 Journal Molecular Vision Section Body Doc Link PMC2890558 Disease Relevance 0 Pain Relevance 0

In analogy to hematopoietic stem cells, solid tumor CSC have been proposed to exhibit high level expression of multidrug transporter family genes, such as ABCG2 and ABCB5, likely resulting in more efficient efflux of chemotherapeutic drugs [13]–[15].

Gene_expression (expression) of ABCG2 in hematopoietic stem cells associated with solid tumor

12) Confidence 0.33 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2413402 Disease Relevance 1.20 Pain Relevance 0

The cellular influx of dasatinib, on the other hand, is not affected by hOCT1 activity, although its efflux may be mediated by ABCB1 and ABCG2.85,86 The intracellular concentration of dasatinib was lower in ABCB1-overexpressing cell lines and was increased in the presence of PSC833, a potent ABCB1 inhibitor.85 The in vitro concentration of dasatinib required to inhibit phosphorylation of CrkL by 50% (dasatinib IC50) was higher in the ABCB1-overexpressing cell lines compared to parental cell lines (100 nM versus 7 nM), and this was reduced to 8 nM with the addition of PSC833.85 Similar results were also seen in the ABCG2-overexpressing cell lines, suggesting that high levels of ABCG2 reduced dasatinib intracellular concentration, leading to an increased dasatinib IC50, which can be modulated with ABCG2 inhibitors.85

Gene_expression (overexpressing) of ABCG2

13) Confidence 0.28 Published 2009 Journal OncoTargets and therapy Section Body Doc Link PMC2886328 Disease Relevance 0.21 Pain Relevance 0

BCRP protein expression was measured flow cytometrically with the monoclonal antibody (mAb) BXP-21.

Gene_expression (expression) of BCRP

14) Confidence 0.28 Published 2009 Journal Oncol. Res. Section Abstract Doc Link 19911699 Disease Relevance 0.34 Pain Relevance 0.28

Hence, we examined the effects of indomethacin and dexamethasone on BCRP expression in MCF cells.

Gene_expression (expression) of BCRP associated with dexamethasone

15) Confidence 0.28 Published 2009 Journal Oncol. Res. Section Abstract Doc Link 19911699 Disease Relevance 0.33 Pain Relevance 0.25

Overexpression of ABC transporters such as Pgp, MRP and BCRP has been shown to be responsible for the major portion of MDR.

Gene_expression (Overexpression) of BCRP

16) Confidence 0.26 Published 2005 Journal Cancer Cell Int Section Body Doc Link PMC1277830 Disease Relevance 0.31 Pain Relevance 0

Imatinib has been reported to be a substrate and/or an inhibitor for the ABCG2 drug efflux pump which is overexpressed in many human tumors and also found to be functionally expressed in CML stem cells.64,83,84 The drug transporter hOCT1 mediates the active transport of imatinib into cells, and inhibition of hOCT1 decreases the intracellular concentration of imatinib, which may predict for a less favorable molecular response.65,66

Gene_expression (overexpressed) of ABCG2 in stem cells associated with myeloid leukemia and cancer

17) Confidence 0.24 Published 2009 Journal OncoTargets and therapy Section Body Doc Link PMC2886328 Disease Relevance 0.32 Pain Relevance 0

Imatinib has been reported to be a substrate and/or an inhibitor for the ABCG2 drug efflux pump which is overexpressed in many human tumors and also found to be functionally expressed in CML stem cells.64,83,84 The drug transporter hOCT1 mediates the active transport of imatinib into cells, and inhibition of hOCT1 decreases the intracellular concentration of imatinib, which may predict for a less favorable molecular response.65,66

Gene_expression (expressed) of ABCG2 in stem cells associated with myeloid leukemia and cancer

18) Confidence 0.24 Published 2009 Journal OncoTargets and therapy Section Body Doc Link PMC2886328 Disease Relevance 0.33 Pain Relevance 0

Dexamethasone downregulates BCRP mRNA and protein expression in breast cancer cell lines.

Gene_expression (expression) of BCRP associated with breast cancer and dexamethasone

19) Confidence 0.24 Published 2009 Journal Oncol. Res. Section Title Doc Link 19911699 Disease Relevance 0.37 Pain Relevance 0.30

It is hypothesized that anti-inflammatory drugs regulate breast cancer resistance protein (BCRP) expression.

Gene_expression (expression) of BCRP associated with inflammation, breast cancer and cinod

20) Confidence 0.21 Published 2009 Journal Oncol. Res. Section Abstract Doc Link 19911699 Disease Relevance 0.34 Pain Relevance 0.22

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