One major impediment to the success of chemotherapy in cancer patients is the risk of developing drug resistance. One mechanism leading to multidrug resistance in cancer therapy is through the ABC transporters. The eukaryotic ABC genes are organized as transporters containing two transmembrane and two ATP binding domains. Alternative splicing is one major mechanism in which a single gene generates functional diversity by producing different spliced isoforms. To determine the variability of ABC transporters, we performed exhaustive search of the NCBI database for ABC transporter genes, in addition to using the Alternative Splicing Annotation Project (ASAP) and the Alternative Splicing Database (ASD). We conducted immunostaining for MRP1 and MDR1 on tissue micro array of 23 breast cancer patients and RNA mediated annealing, selection, extension and ligation (RASL) assay for analysis of mRNA splicing isoforms which was performed on exon/exon target. Tumor cells from chemotherapy resistant patients show specific expression patterns of drug-resistant ATP-binding cassette transporter. Our data showed alternative splicing in 3 and 4 exon/exon borders in MDR1 and PGP genes. Two splicing events in MDR1 and one in PGP transcripts were predicted to be alternatively spliced in ASAP database. Interestingly, exon11/12 border in MDR1 is found to be alternatively spliced. In summary, protein microarray analysis demonstrated significant correlation between MRP1 expression and survival rate within 5 years. In contrast, MDRI protein expression did not correlate with 5 year survival rate. This may be due to variations in the MDR1 isoforms.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3531.

©2010 American Association for Cancer Research
2010