Z01 BC 005725 (Z01) | |||
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Title | ABC Transporters in Human Disease and Multidrug Resistance | ||
Institution | NCI, Bethesda, MD | ||
Principal Investigator | Dean, Michael | NCI Program Director | N/A |
Cancer Activity | N/A | Division | CCR |
Funded Amount | $505,750 | Project Dates | 10/01/1992 - N/A |
Fiscal Year | 2007 | Project Type | Intramural |
Research Topics w/ Percent Relevance | Cancer Types w/ Percent Relevance | ||
N/A |
Breast (10.0%) Eye (10.0%) Lung (10.0%) Pancreas (10.0%) Prostate (10.0%) Stomach (10.0%) Urinary System (10.0%) |
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Research Type | |||
Interactions of Genes and/or Genetic Polymorphisms with Exogenous and/or Endogenous Factors Resources and Infrastructure Related to Etiology |
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Abstract | |||
The ABC gene family code for transporter proteins pumping a variety of compounds across the membranes of cells and tissues. Overexpression of ABC transporters is an important cause of multidrug resistance to chemotherapy agents and these genes are mutated in diverse human diseases. To understand the function of the <I>ABCC6</I> gene causing pseudoxanthoma elasticum we have initiated a metabolomics study. Urine from male patients has been used to generate metabolite profiles. We have also initiated studies of serum and urine from <I>Abcc6</I> -/- mice and from yeast cell deficient in an ABCC subfamily gene. These studies should aid us in identifying the substrate of this transporter. <I>ABCG2</I> is an important drug resistance gene and we have screened for and identified new inhibitors. One of these is a new class of compounds known as botrylamides. The botrylamides are found in marine sponges and are simple enough chemically that derivatives can be synthesized and a structure/function relationship determined. <I>ABCG2</I> is an important marker and resistance factor in cancer stem cells. Several of these compounds can be shown to inhibit substrate binding and/or ATPase activity of the protein. The complete complement of ABC genes was characterized in the sea urchin, a major model organism for development and cell biology. We find that the sea urchin has a dramatically expanded complement of drug transporter genes as well as orthologs of many human disease genes. |