Elucidate the Function and Expression of Prostate Derived Ets Factor in the Human Prostate and Bladder

Project: National Science and Technology CouncilNational Science and Technology Council Academic Grants

Project Details


The prostate derived ets factor (PDEF) is one of the Ets family genes which 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. The regulatory mechanisms of PDEF gene in the human prostate and bladder carcinoma are still unknown. Studies using RT-PCR and immunoblot assays revealed that PDEF expresses in prostate and bladder carcinoma cells in cell specific pattern. The PDEF acts as an androgen-independent transcriptional activator of the prostate specific antigen (PSA) promoter. Forced-overexpression of PDEF dramatically enhances PSA gene expression determined by semi-quantitative RT-PCR, enzyme linked immunosorbent assay (ELISA), immunoblot, and transient gene expression assays. The preliminary studies revealed that digitalis glycosides inhibit the PSA gene expression through the down-regulation of gene expression of PDEF in LNCaP cells. Results from 3H-thymidine incorporation assay and matrigel invasion assay indicated that stably-overexpression of PDEF in LNCaP cells attenuated proliferation and invasion ability of the cells. Results from semi-quantitative RT-PCR, immunoblot assay, and transient gene expression assay revealed that PDEF enhances gene expression of B-cell translocation gene 2 (BTG2, an antiproliferatoin gene), N-myc downstream regulated gene 1 (NDRG1, a tumor metastasis suppressor gene), and Maspin (a serpin with tumor suppressor gene), which may account for the function of PDEF in proliferation and invasion in LNCaP cells. Result from in vitro and in vitro studies revealed that stably-overexpression of PDEF in bladder carcinoma cells (BFTC 905) promoted cell proliferation and tumorigenesis but blocks cell migration and invasion. It seems that PDEF has divergent functions in different cells. The objectives of this three-year proposal are to (1) understand and characterize the function of PDEF gene in the prostate and bladder carcinogenesis, (2) determine and characterize the promoter/enhancer response element on the PDEF gene, and (3) understand the regulatory mechanisms of the PDEF on oncogenes in prostate and bladder carcinoma cells. The regulators will be investigated in this proposal include p53, bioflavonoids, retinol acid, steroid, and anticancer drugs. The long-term objects of this proposal are to understand the regulatory mechanisms of PDEF gene in the neoplasia of the prostate and bladder, and to employ these concepts in the early diagnosis, drug screen, and gene therapy of the disease of prostate and bladder carcinoma.

Project IDs

Project ID:PC9801-2485
External Project ID:NSC97-2320-B182-023-MY3
Effective start/end date01/08/0931/07/10


  • prostate
  • PDEF
  • PSA
  • bladder
  • BTG2
  • NDRG1
  • Maspin
  • p53
  • bioflavonoid
  • steroid


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