Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P33527 (ABCC1)
 1,164 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

MUC1 (CD227), a membrane tethered mucin glycoprotein, is overexpressed in >60% of human pancreatic cancers (PCs), and is associated with poor prognosis, enhanced metastasis and chemoresistance. The objective of this study was to delineate the mechanism by which MUC1 induces drug resistance in human (BxPC3 and Capan-1) and mouse (KCKO, KCM) PC cells. We report that PC cells that express high levels of MUC1 exhibit increased resistance to chemotherapeutic drugs (gemcitabine and etoposide) in comparison with cells that express low levels of MUC1. This chemo resistance was attributed to the enhanced expression of multidrug resistance (MDR) genes including ABCC1, ABCC3, ABCC5 and ABCB1. In particular, levels of MRP1 protein encoded by the ABCC1 gene were significantly higher in the MUC1-high PC cells. In BxPC3 and Capan-1 cells MUC1 upregulates MRP1 via an Akt-dependent pathway, whereas in KCM cells MUC1-mediated MRP1 upregulation is via an Akt-independent mechanism. In KCM, BxPC3 and Capan-1 cells, the cytoplasmic tail motif of MUC1 associates directly with the promoter region of the Abcc1/ABCC1 gene, indicating a possible role of MUC1 acting as a transcriptional regulator of this gene. This is the first report to show that MUC1 can directly regulate the expression of MDR genes in PC cells, and thus confer drug resistance.
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PMID:MUC1 induces drug resistance in pancreatic cancer cells via upregulation of multidrug resistance genes. 2377 63

P-glycoprotein (P-gp/ABCB1) and multidrug resistance-associated protein 1 (MRP1/ABCC1) are the main drug efflux transporters associated with treatment failure in cancer. Much attention has been focused on the molecular mechanisms regulating the expression of these transporters as a viable approach for identifying novel drug targets in circumventing cancer multidrug resistance (MDR) clinically. In this paper, we examine the role of miR-326 in the context of its intercellular transfer between cancer cells by extracellular membrane vesicles called microparticles (MPs). We observe that cellular suppression of ABCC1 by miR-326 is modulated by the presence of ABCB1 transcript. Specifically, we show that siRNA silencing of MP-transferred ABCB1 transcript reverses the knockdown effects of miRNA-326 on target MRP1/ABCC1 transcripts. We also demonstrate a dominance of ABCB1 transcripts when co-localized with ABCC1 transcripts, which is consistent with the facilitation of miR-326 function by ABCB1. This study identifies a novel pathway regulating the expression of ABC transporters and positions ABCB1 mRNA as a transcriptional regulator of other members of this superfamily in multidrug resistant cells through its actions on miRNAs.
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PMID:A novel mechanism governing the transcriptional regulation of ABC transporters in MDR cancer cells. 2805 Aug 91