Functions of Beta- and Gamma-Catenins in Prostate Cancer
Final rept. 1 Aug 1998-31 Jan 2001
BURNHAM INST LA JOLLA CA
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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 APCcatenin complex, and regulates the ubiquitin-dependent turnover of beta-catenin through a novel previously unidentified mechanism. We also showed that this pathway is linked to genotoxic injury DNA damage responses involving p53, an important tumor suppressor. To understand the in vivo relevance of Siah-1 interactions with the APCcatenin complex, we proposed generating transgenic mice that express genes which modulate this pathway in the prostate gland, thus providing new insights to prostate cancer pathogenesis and metastasis.
- Anatomy and Physiology
- Medicine and Medical Research