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)

We investigated the relationship of ABCB1/MDR1, ABCC1/MRP1 and ABCG2/BCRP expression and promoter methylation with pancreatic cancer tumorigenesis and drug resistance. Gemcitabine-resistant pancreatic cancer cells, SW1990/GZ (33.3-fold increased resistance), were obtained by treating SW1990 cells with gemcitabine. The expression of ABCB1/MDR1, ABCC1/MRP1 and ABCG2/BCRP was determined by quantitative real-time RT-PCR in the cell lines, 3 normal pancreatic tissues, 15 human pancreatic cancer samples and 15 adjacent tissues. Promoter methylation was determined in cell lines by bisulfite genomic sequencing. ABCB1/MDR1, ABCC1/MRP1 and ABCG2/BCRP were upregulated in SW1990 and SW1990/GZ compared with normal pancreatic tissue, and expression in SW1990/GZ was significantly higher than in SW1990 cells. ABCB1/MDR1, ABCC1/MRP1 and ABCG2/BCRP were upregulated in pancreatic cancer tissues, compared to adjacent tissues. The ABCB1/MDR1, ABCC1/MRP1 and ABCG2/BCRP promoter were hypomethylated in all the cell lines. ABCB1/MDR1, ABCC1/MRP1 and ABCG2/BCRP expression correlated with pancreatic cancer tumorigenesis and drug resistance in a mechanism that is independent of promoter methylation.
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PMID:Expression and promoter methylation analysis of ATP-binding cassette genes in pancreatic cancer. 2195 51

Genetic polymorphisms in ABC (ATP-binding cassette) transporter genes are associated with differential responses to chemotherapy in various cancers including pancreatic cancer. In this study, four SNPs in the ABCB1, ABCC1, and ABCG2 genes were investigated in normal and pancreatic cancerous specimens. The expression of the three transporters was also analyzed. The TT genotypes of G2677T and C3435T in ABCB1 gene were associated with lower risk of developing pancreatic cancer (P = 0.013, OR = 0.35 and P = 0.015, OR = 0.29, resp.). To our knowledge, this is the first report of the common polymorphisms in the ABCB1 gene affecting the genetic risk of developing pancreatic cancer. Moreover, the expression of ABCB1 in 2677TT and 3435TT carriers was lower compared to the wild-type homozygotes and heterozygotes. A cell viability assay, using standard pancreatic cancer cell lines, revealed that the ABCB1 2677TT-3455TT haplotype was more sensitive than the other haplotypes to gemcitabine. Conclusion. Polymorphisms in ABCB1 G2677T and G3435T were associated with differential susceptibility to pancreatic cancer and may predict responses to chemotherapy.
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PMID:ATP-Binding Cassette Genes Genotype and Expression: A Potential Association with Pancreatic Cancer Development and Chemoresistance? 2488 56

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and protein synthesis. To characterize functions of miRNAs and to assess their potential applications, we carried out an integrated multi-omics analysis to study miR-145, a miRNA that has been shown to suppress tumor growth. We employed gene expression profiling, miRNA profiling and quantitative proteomic analysis of a pancreatic cancer cell line. In our transcriptomic analysis, overexpression of miR-145 was found to suppress the expression of genes that are implicated in development of cancer such as ITGA11 and MAGEA4 in addition to previously described targets such as FSCN1, YES1 and PODXL. Based on miRNA profiling, overexpression of miR-145 also upregulated other miRNAs including miR-124, miR-133b and miR-125a-3p, all of which are implicated in suppression of tumors and are generally co-regulated with miR-145 in other cancers. Using the SILAC system, we identified miR-145-induced downregulation of several oncoproteins/cancer biomarkers including SET, RPA1, MCM2, ABCC1, SPTBN1 and SPTLC1. Luciferase assay validation carried out on a subset of downregulated candidate targets confirmed them to be novel direct targets of miR-145. Overall, this multi-omics approach provided insights into miR-145-mediated tumor suppression and could be used as a general strategy to study the targets of individual miRNAs.
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PMID:Identification of miR-145 targets through an integrated omics analysis. 2535 83