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)

EGFR mutations have been correlated to responsiveness to treatment with tyrosine kinase inhibitors. These drugs are themselves substrates for ABC transporters. In the present work we describe the immunohistochemical profile of an archival sample from a male Brazilian patient with no Asian ancestry and never smoker, diagnosed with non-small cell lung cancer. This tumor was found to contain an in-frame hemi- or homozygous deletion, E746-A750 in exon 19 of the EGFR gene. Immunohistochemistry revealed a relatively weak staining for the ABC transporter subfamily ABCC1 and strongly for ABCB1. The cytoplasm stained positively for Bax and the nucleus stained for p53, but was negative for Bcl-2. Antibody against acetylated lysine revealed staining in both, cytoplasm and nucleus of tumor cells in contrast to normal cells which were essentially negative. The overall immunohistochemistry pattern obtained for this sample indicates that the del E746-A750 mutation may have down-regulated the expression of ABCC1. The results also suggest that the NSCLC analyzed displayed a transcriptionally active chromatin as judged by the results obtained with the anti-acetylated lysine antibody.
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PMID:Expression of ABC transporters, p53, Bax, Bcl-2 in an archival sample of non-small cell lung cancer bearing a deletion in the EGFR gene. 1936 Mar 19

Histone deacetylase (HDAC) inhibitors and DNA alkylators are effective components of combination chemotherapy. The aim of the present study was to investigate the possible mechanism of their synergism by detecting the effect of HDAC inhibitors on the expression levels of drug transporters that export DNA alkylators. It was demonstrated that the HDAC inhibitor sodium butyrate (NaB) induced the differential expression of multidrug resistant ATP-binding cassette (ABC) transporters in lung cancer and colorectal cancer cells. Specifically, NaB increased the mRNA expression levels of ABC subfamily B member 1 (ABCB1), ABCC10 and ABCC12, and protein expression levels of multidrug resistance-1 (MDR1), multidrug resistance-associated protein 7 (MRP7) and MRP9. Moreover, NaB decreased the expression levels of ABCC1, ABCC2 and ABCC3 mRNAs, as well as those of MRP1, MRP2 and MRP3 proteins. The molecular mechanism underlying this process was subsequently investigated. NaB decreased the expression of HDAC4, but not HDAC1, HDAC2 or HDAC3. In addition, NaB promoted histone H3 acetylation and methylation at lysine 9, as well as MDR1 acetylation, suggesting that acetylation and methylation may be involved in NaB-mediated ABC transporter expression. Thus, the present results indicated that the synergism of the HDAC inhibitors with the DNA alkylating agents may due to the inhibitory effect of MRPs by HDAC inhibitors. The findings also suggested the possibility of antagonistic effects following the combined treatment of HDAC inhibitors with MDR1 ligands.
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PMID:Effect of sodium butyrate on ABC transporters in lung cancer A549 and colorectal cancer HCT116 cells. 3293 16