| Summary: | 碩士 === 長庚大學 === 基礎醫學研究所 === 95 === The PDEF is one of the Ets family genes. The Ets family proteins are regarded as transcription factors regulating a number of biological processes including cell proliferation, differentiation, and invasion and are thought to play an important role in oncogenesis. Several previous studies showed PDEF potently mediates migration in normal mammary cell and breast cancer cell lines; however, the regulatory mechanisms of PDEF gene in the prostate and bladder are still unknown. Our studies using RT-PCR and immunoblot assays revealed that PDEF expresses in prostate cancer cell lines and some of bladder carcinoma cell lines. The objectives of this thesis are to (1) understand and characterize the function of PDEF gene in the prostate carcinogenesis, (2) understand and characterize the function of PDEF gene in the bladder carcinogenesis, (3) understand the regulatory mechanisms of the PDEF gene. Our studies revealed that digitalis glycosides, silibinin, and luteolin inhibit the PSA gene expression through the down-regulation of gene expression of PDEF in LNCaP cells. However, curcumin blocks the expressions of androgen receptor but not PDEF which attenuates PSA gene expression. In vivo and in vitro studies indicated that stably-overexpression of PDEF in prostate carcinoma cells (DU145) or bladder carcinoma cells (BFTC 905) promotes cell proliferation and tumorigenicity. PDEF enhances in vitro migration and invasion of DU145 cells; on the contrary, overexpressed PDEF blocks cell migration and invasion in BFTC 905 cells. Moreover, Stably-overexpressed PDEF in the LNCaP cells attenuates in vitro cell proliferation and invasion. Transient gene expression assays revealed that resveratrol and vitamin A upregulates PDEF gene expression in LNCaP cell; however, forced p53 overexpression blocked PDEF gene expression in PC-3 cells. Our studies provide the evidences to understand the regulatory mechanisms of PDEF gene in the neoplasia of the prostate and bladder. The divergent functions of PDEF in different cells may provide new concepts in the early diagnosis, drug screen, and gene therapy of the disease of prostate and bladder carcinoma.
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