INT302180

Context Info Confidence 0.61 First Reported 2009 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 6 Total Number 6 Disease Relevance 3.13 Pain Relevance 0.43

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

Anatomy Link Frequency stem cells 4 lens 2 Abcg2 (Mus musculus)

Pain Link Frequency Relevance Heat methotrexate 70 98.96 Calcium channel 2 89.76 COX-2 inhibitor 52 64.08 Arthritis 27 50.00 Inflammation 28 14.80 cINOD 17 5.00 Central nervous system 14 5.00 cytokine 14 5.00 antagonist 12 5.00 adenocard 8 5.00

Disease Link Frequency Relevance Heat Breast Cancer 59 99.92 Cancer 239 99.40 Rheumatoid Arthritis 13 98.44 Myeloid Leukemia 171 97.24 Apoptosis 156 96.26 Advanced Or Metastatic Breast Cancer 15 95.12 Recurrence 16 94.40 Toxicity 36 80.56 Malignant Neoplastic Disease 4 67.52 Head & Neck Cancer 2 65.44

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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].

Positive_regulation (upregulation) of Gene_expression (expression) of ABCG2 associated with cancer and methotrexate

1) Confidence 0.61 Published 2010 Journal Human Genomics and Proteomics : HGP Section Body Doc Link PMC2958653 Disease Relevance 0.34 Pain Relevance 0.30

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

Positive_regulation (levels) of Gene_expression (express) of ABCG2 in lens

2) Confidence 0.57 Published 2010 Journal Molecular Vision Section Body Doc Link PMC2890558 Disease Relevance 0 Pain Relevance 0.04

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].

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

3) Confidence 0.49 Published 2010 Journal International Journal of Cell Biology Section Body Doc Link PMC2841246 Disease Relevance 0.95 Pain Relevance 0.09

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].

Positive_regulation (resistance) of Gene_expression (expression) of ABCG2 in CSCs

4) Confidence 0.34 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2860989 Disease Relevance 1.31 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

Positive_regulation (overexpressing) of Gene_expression (overexpressing) of ABCG2

5) Confidence 0.22 Published 2009 Journal OncoTargets and therapy Section Body Doc Link PMC2886328 Disease Relevance 0.21 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

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

6) Confidence 0.19 Published 2009 Journal OncoTargets and therapy Section Body Doc Link PMC2886328 Disease Relevance 0.32 Pain Relevance 0

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