Project Details
Abstract
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:PC9709-0929
External Project ID:NSC97-2320-B182-023-MY3
External Project ID:NSC97-2320-B182-023-MY3
Status | Finished |
---|---|
Effective start/end date | 01/08/08 → 31/07/09 |
Keywords
- prostate
- PDEF
- PSA
- bladder
- BTG2
- NDRG1
- Maspin
- p53
- bioflavonoid
- steroid
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