A New APC-Like Gene Involved in regulation of B-catenin/LEF
Abstract
Here we describe two different approaches to better understanding the functions of Wnt and TGF-B signaling in cancer pathogenesis. First, we have identified a second adenomatous polyposis coli (APC)-like gene, APC2/APCL. Interphase fluorescence in situ hybridization analysis revealed an APC2 allelic imbalance in 19 of 20 ovarian cancers screened and indicates that APC2 could be a potential tumor suppressor gene in ovarian cancer. Antibodies against the NH2 terminus of human APC2 show that endogenous APC2 is diffusely distributed in the cytoplasm and colocalizes with both the Golgi apparatus and actin filaments. Second, we have identified a protein that interacts with the intracellular domain of the TGF-B receptor BMPRlA. This protein, known as SAP49, is a developmentally- regulated splicing factor. The interaction was identified in a yeast two-hybrid analysis and confirmed via immunoprecipitation/Western Blot analysis in transfected human cells. The interaction has been localized to the GS-domain of BMPRlA and the proline rich- domain of SAP49 via mutational analysis. Further studies will address the biological relevance of the interaction in human cancer pathogenesis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2003
- Accession Number
- ADA421991
Entities
People
- Tagvor G. Nishanian
- Todd Waldman
Organizations
- Georgetown University