Functions of Beta- and Gamma-Catenins in Prostate Cancer
Abstract
Contact among cells in epithelia plays an important role in regulating cell growth and migration. Cell-cell contact generally suppresses cell division and limits migration, while disruption of cell-cell interactions stimulates cell cycle entry and permits migration. A multiprotein complex relays information about cell-cell contact at the plasma membrane into the nucleus, affecting the expression of genes important for cell division. This protein complex includes the catenins and the tumor suppressor APC. Mutations that dysregulate catenins or that inactive APC occur commonly in epithelial malignancies. We recently discovered that the protein Siah-1 interacts with the APC/catenin complex, and regulates the ubiquitin-dependent turnover of gamma-catenin through a novel previously unidentified mechanism. To understand the in vivo relevance of Siah-l interactions with the APC/catenin complex, we are generating transgenic mice that express Siah-l or a mutant of Siah-l, which interferes with the function of the endogenous wild- type protein in the prostate gland. Studies of these mice will address the role of Siah in the regulation of prostate cancer pathogenesis and metastasis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 1999
- Accession Number
- ADA386828
Entities
People
- John C. Reed
Organizations
- Sanford Burnham Prebys Medical Discovery Institute