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)

Multidrug resistance may be conferred by P-glycoprotein (Pgp, ABCB1) or the multidrug resistance associated protein (MRP). These membrane proteins are members of the ATP binding cassette transporter superfamily and are responsible for the removal from the cell of several anticancer agents including doxorubicin. Modulators can inhibit these transporters. LY335979 is among the most potent modulators of Pgp with a Ki of 59 nM. LY335979 is selective for Pgp, and does not modulate MRP-mediated resistance by MRP1 (ABCC1) and MRP2 (ABCC2). LY335979 significantly enhanced the survival of mice implanted with Pgp-expressing murine leukemia (P388/ADR) when administered in combination with either daunorubicin, doxorubicin or etoposide. Coadministration of LY335979 with paclitaxel compared to paclitaxel alone significantly reduced the tumor mass of the Pgp-expressing UCLA-P3.003VLB lung carcinoma in a xenograph model and delayed the development of tumors in mice implanted with the parental drug-sensitive UCLA-P3 tumor. LY335979 was without significant effect on the pharmacokinetics of these anticancer agents. This may be due impart to its poor inhibition of four major cytochrome P450 isozymes important in metabolizing doxorubicin and other oncolytics. The selectivity and potency of this modulator allows the clinical evaluation of the role of Pgp in multidrug resistance. LY335979 is currently in clinical trials.
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PMID:Reversal of multidrug resistance by the P-glycoprotein modulator, LY335979, from the bench to the clinic. 1117 91

The ATP binding cassette transporter subtype A5 (ABCA5)-like transporters ABCA5, ABCA6, ABCA8, ABCA9 and ABCA10 form a unique gene cluster within the ABC transporter superfamily, though their function is still poorly understood. The purpose of this study is to examine whether ABCA5-like transporters may play a role in tumor development by measuring their mRNA levels in human tissues and tumors. Intense mRNA expression of human ABCA5-like transporters was detected in the brain. ABCA5 and ABCA8 mRNAs were detected in spleen, testis and ovary. ABCA5 mRNA was also detected in liver and pancreas. ABCA6 mRNA was detected in lung and liver, and ABCA8 was detected in lung. ABCA6, ABCA7 and ABCA8 mRNAs were not detected in any tumors, but weak mRNA expression of ABCA10 was detected in all tumors examined. ABCA5 mRNA was detected in poorly differentiated colon adenocarcinoma (GI-112) and undifferentiated ovarian carcinoma (GI-102), but not in normal colon. ABCB1 mRNA was also detected in GI-112, while ABCC1 and ABCA2 mRNAs were not. In contrast, ABCC1 and ABCA2 mRNAs, but not ABCA5 or ABCB1 mRNA, were detected in well differentiated colon adenocarcinoma (CX-1). Thus, induction of ABCA5, together with ABCB1, appears to be correlated with the differentiation state of human colon tumors, and may have a role in tumor development.
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PMID:Correlation of induction of ATP binding cassette transporter A5 (ABCA5) and ABCB1 mRNAs with differentiation state of human colon tumor. 1754 Nov 69

Dendritic cells (DCs) play a pivotal role in the development of cutaneous contact hypersensitivity (CHS) and atopic dermatitis as they capture and process antigen and present it to T lymphocytes in the lymphoid organs. Recently, it has been indicated that a topical application of the sphingolipid sphingosine 1-phosphate (S1P) prevents the inflammatory response in CHS, but the molecular mechanism is not fully elucidated. Here we indicate that treatment of mice with S1P is connected with an impaired antigen uptake by Langerhans cells (LCs), the initial step of CHS. Most of the known actions of S1P are mediated by a family of five specific G protein-coupled receptors. Our results indicate that S1P inhibits macropinocytosis of the murine LC line XS52 via S1P(2) receptor stimulation followed by a reduced phosphatidylinositol 3-kinase (PI3K) activity. As down-regulation of S1P(2) not only diminished S1P-mediated action but also enhanced the basal activity of LCs on antigen capture, an autocrine action of S1P has been assumed. Actually, S1P is continuously produced by LCs and secreted via the ATP binding cassette transporter ABCC1 to the extracellular environment. Consequently, inhibition of ABCC1, which decreased extracellular S1P levels, markedly increased the antigen uptake by LCs. Moreover, stimulation of sphingosine kinase activity, the crucial enzyme for S1P formation, is connected not only with enhanced S1P levels but also with diminished antigen capture. These results indicate that S1P is essential in LC homeostasis and influences skin immunity. This is of importance as previous reports suggested an alteration of S1P levels in atopic skin lesions.
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PMID:Sphingosine 1-phosphate modulates antigen capture by murine Langerhans cells via the S1P2 receptor subtype. 2314 72