Abstract 1693: Mrp7 as a breast cancer resistance factor

Abstract

Abstract Breast cancer is the most common cancer and the second leading cause of cancer deaths in American women. Breast cancer kills more than 40,000 women every year in the United States. Taxanes and epothilone B are used to treat breast cancer, but cellular resistance to chemotherapeutic agents is a major obstacle. Therapy-induced overexpression of ATP-binding cassette (ABC) drug efflux pumps promotes resistance in many drug-treated cancers. While early studies focused on overexpression and activity of the P-glycoprotein (Pgp) pump, a structurally distinct group of ABC efflux pumps, known as the Multidrug Resistance Proteins (MRPs), have been gaining increasing attention as alternative sources of resistance. There are 9 MRP family members (MRP1-9), with each family member preferentially transporting somewhat overlapping groups of substrates. We have previously shown that MRP7 is distinct from other MRPs because MRP7 confers resistance to a wide variety of anticancer agents including taxanes, vinca alkaloids and nucleoside-based analogs. We also have evidence that Mrp7 null mice are sensitized to taxanes (submitted). We bred a mammary tumor model to our Mrp7 null mouse to investigate Mrp7's in vivo activities regarding breast cancer resistance mechanisms. To better understand the resistance mechanisms of MRP7 the expression level of Mrp7 and expression levels of other transporters was determined in these cell lines using qRT-PCR. In addition, cell lines derived from mammary tumors are being evaluated to determine the impact Mrp7 has on sensitization to agents used in the treatment of breast cancer: epothilone B, docetaxel and paclitaxel. Further, the growth properties of these mammary tumor cell lines will be characterized. Lastly, to better understand the physiological role of this efflux pump, MRP7 cellular localization and polarity are being investigated. Further research into previously mentioned aims and specific MRP7 inhibitors will aid in combating cellular resistance to chemotherapeutic agents. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1693. doi:10.1158/1538-7445.AM2011-1693