Prostate cancer is the most common malignancy in North American men. However, the genetic events associated with the malignant transformation of prostatic cells are largely unknown. Identification of new prostate specific genes could provide new markers and could be instrumental for development of new treatment modalities. Tensin is a focal adhesion molecule that interacts with the actin cytoskeleton and mediates signal transduction. During the course of isolating tensin family genes, we have identified a novel C-terminal tensin-like molecule, cten. Cten is a 715 amino acid molecule containing src homology 2 and phosphotyrosine-binding domains that are similar to tensins. However, cten does not have the actin-binding activities found in tensin family and is much smaller in molecular mass. Interestingly, the expression of cten is restricted to prostate and placenta, and is often reduced/lost in prostate cancer/cell lines. In addition, human cten gene is located on chromosome 17q21, a region often deleted in prostate cancer. Cten localizes to focal adhesions, but unlike tensins, it is also found in nucleus. We hypothesize that cten is a prostate-specific tumor suppressor that plays an important role in signaling between focal adhesions and the nucleus; and that alteration of cten expression or function disrupts its normal actions and increases the risk for prostate cancer. The overall goal of this proposal is to determine whether the expression of cten can be used in early detection, diagnosis and monitoring of disease progression, and to study the function of cten in prostate cancer. There are three specific aims:
Aim 1. To establish the value of cten expression patterns in prostate cancer diagnosis and prognosis.
Aim 2. To determine the role of cten on the phenotype of prostate cancer cells, and elucidate the functions of its subcellular localization, using in vitro model systems.
Aim 3. To determine the function of cten in prostate physiology and carcinogenesis, using in vivo models of transgenic mice expressing wild-type or mutated human cten.
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