The Promoter or A Prostate Specific Gene, Cten

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DESCRIPTION (provided by applicant): Prostate is a collection of branched tubuloalveolar glands. Benign prostatic hyperplesia is commonly detected in elder men and prostate cancer is the most common malignancy in North American and European men. However, the genetic events associated with the malignant transformation and hypertrophy 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. 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 in men, and is often reduced/lost in prostate cancer/cell lines. These data suggest that cten plays an important role in the prostate gland. Alteration of cten expression disrupts its normal function and increases the risk for prostate cancer. In this proposal we want to test the hypothesis that the prostate-specific expression of cten is regulated by the DNA sequence 5' upstream of the transcription initiation site of cten gene. There are three specific aims in this proposal: Aim 1. Isolation and characterization of the 5' flanking DNA of the human cten gene. Aim 2. Analysis of the promoter activity of the cten gene. Aim 3. Generation and characterization of transgenic mice expressing GFP-cten driven by cten promoter. These studies will lead to a better understanding of the mechanism that regulates the expression of human cten gene, the identification of the prostate-specific cten promoter for expression of transgenes in the prostate gland, and the function of cten in mouse prostate.