The ATP-binding cassette (ABC) gene family encodes a diverse group of transporter proteins that pump a wide variety of compounds across the membranes of cells and tissues. Several human ABC transporters are overexpressed in tumor cells that are resistant to chemotherapy drugs. In addition, several ABC genes ( CFTR , SUR , ALDP ) are mutated in inherited diseases. Previous work with DCS scientists showed that the MXR/ABCP gene is overexpressed in tumor cell lines that are resistant to mitoxantrone, topotecan and several other drugs. We have now shown that the gene is expressed in the trophoblast cells of the placenta and may play a role in transport of substances into or out of the fetus. Characterization of additional expressed sequences from the human genome demonstrates that there are at least 55 ABC genes. One of these genes ABCG5 is expressed exclusively in the liver and is mutated in a sterol transport disorder. We also demonstrated that the ABCA1 gene is the gene responsible for Tangier disease, a disorder of cholesterol transport. Together these two findings will provide considerable insight into how cholesterol is absorbed by the intestine, transported from peripheral tissues, and excreted. Preliminary data suggests that other ABC genes my be involved in cis-platinum resistance.
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