The Role of Alternative Splicing in Breast Cancer Progression
Abstract
Alternative pre-mRNA splicing generates thousands of different mRNA isoforms in metazoan organisms. It is unknown if breast-cancer associated alternative splicing is regulated like tissue-specific splicing, or whether it is caused by changes in the splicing accuracy. To test the hypothesis that the accuracy of the spliceosome is compromised in breast tumor cells, we have designed a quantitative real-time PCR assay to determine the number of incorrectly spliced mRNA products made from pre-mRNA transcripts that produce only a single mRNA product in all eukaryotic genomes. Analysis of all possible alternative exon exclusion patterns for these genes demonstrates that in some cases a splicing mistake is made only once in 25,000 intron removal events. These results demonstrate that the error rate of the spliceosome is extremely low. Using this assay we examined splicing error rates in breast cancer cell lines. Using matched cancer and normal cell lines we demonstrated that breast cancer cell lines exhibit an up to 3-fold decrease in the number of splicing errors. We conclude that perturbed pre-mRNA splicing in breast cancer is mediated in part through alterations of the intrinsic fidelity of the spliceosome.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2007
- Accession Number
- ADA477333
Entities
People
- Klemens J. Hertel
Organizations
- University of California, Irvine