Regulation of Alternative Splicing in Tumor Metastasis
Abstract
The primary goal of the Idea Award research is to develop methods for the identification of factors that influence the regulation of splicing in breast cancers. During the 1st year of research funded by this grant, we developed assays for the isolation and characterization of serine-arginine-(SR)-repeat proteins, and associated factors, SR proteins are important for both constitutive and regulated pre-mRNA splicing. Our work has resulted in the identification of the oncoprotein DEK as an SR-associated protein that assembles into splicing complexes. Although our studies did not reveal a function for DEK in splicing, we made the interesting observation that this protein forms a splicing-dependent interaction with mRNA. In conjunction with concurrent studies on SRml60 (the SR-related nuclear matrix protein of 160 kDa) splicing coactivator, which associates with DEK, our results suggest that DEK may be involved in the splicing-dependent promotion of mRNA export from the nucleus, These results are summarized in the first pan of this report. We have also initiated the development of an exon microarray for the large-scale analysis of alternative splicing profiles. A major application of this new technology will be the identification of aberrant alternative splicing events that are specifically associated with breast cancer. The development of an exon microarray will ultimately provide new information on the factors that influence the "global" regulation and coordination of alternative splicing events, and may lead to the identification of breast cancer-specific alternative splicing events. This approach may. therefore, provide a valuable route towards the identification of new factors that facilitate the diagnosis, typing and, ultimately, the treatment of breast cancers.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2000
- Accession Number
- ADB267958
Entities
People
- Benjamin J. Blencowe
Organizations
- University of Toronto