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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA102537-01A1
Application #
6778867
Study Section
Tumor Cell Biology Study Section (TCB)
Program Officer
Sussman, Daniel J
Project Start
2004-04-01
Project End
2009-03-31
Budget Start
2004-04-01
Budget End
2005-03-31
Support Year
1
Fiscal Year
2004
Total Cost
$233,598
Indirect Cost
Name
University of California Davis
Department
Orthopedics
Type
Schools of Medicine
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618
Yang, Kuan; Wu, Wei-Ming; Chen, Ya-Chi et al. (2016) ?Np63? Transcriptionally Regulates the Expression of CTEN That Is Associated with Prostate Cell Adhesion. PLoS One 11:e0147542
Hong, Shiao-Ya; Shih, Yi-Ping; Sun, Peng et al. (2016) Down-regulation of tensin2 enhances tumorigenicity and is associated with a variety of cancers. Oncotarget 7:38143-38153
Shih, Yi-Ping; Sun, Peng; Wang, Aifeng et al. (2015) Tensin1 positively regulates RhoA activity through its interaction with DLC1. Biochim Biophys Acta 1853:3258-65
Lo, Su Hao (2014) C-terminal tensin-like (CTEN): a promising biomarker and target for cancer. Int J Biochem Cell Biol 51:150-4
Hung, Shih-Ya; Shih, Yi-Ping; Chen, Michelle et al. (2014) Up-regulated cten by FGF2 contributes to FGF2-mediated cell migration. Mol Carcinog 53:787-92
Chen, Nien-Tsu; Kuwabara, Yasuko; Conley, Christopher et al. (2013) Phylogenetic analysis, expression patterns, and transcriptional regulation of human CTEN gene. Gene 520:90-7
Hong, Shiao-Ya; Shih, Yi-Ping; Li, Tianhong et al. (2013) CTEN prolongs signaling by EGFR through reducing its ligand-induced degradation. Cancer Res 73:5266-76
Li, Jie-Ren; Shi, Lifang; Deng, Zhao et al. (2012) Nanostructures of designed geometry and functionality enable regulation of cellular signaling processes. Biochemistry 51:5876-93
Shih, Yi-Ping; Takada, Yoshikazu; Lo, Su Hao (2012) Silencing of DLC1 upregulates PAI-1 expression and reduces migration in normal prostate cells. Mol Cancer Res 10:34-9
Lin, Y; Chen, N-T; Shih, Y-P et al. (2010) DLC2 modulates angiogenic responses in vascular endothelial cells by regulating cell attachment and migration. Oncogene 29:3010-6

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