Functions of Beta- and Gamma-Catenins in Prostate Cancer
Annual rept. 1 Aug 1998-31 Jul 1999
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 gamma-catenin through a novel previously unidentified mechanism. To understand the in vivo relevance of Siah-l interactions with the APCcatenin 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.
- Anatomy and Physiology
- Medicine and Medical Research