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Previous studies have shown that human PSP94 can inhibit the growth of prostate cancer cells both in vitro and in vivo. To further validate this potential and investigate the protein within a homologous setting, we examined the effects of rat PSP94 on the growth of the rat prostate adenocarcinoma cell line PAIII in vitro. To generate rat PSP94, we used both a plasmid-based expression system and a recombinant rat PSP molecule. Rat PSP was shown to inhibit the growth and survival of PAIII cells in a dose-dependent manner with > 90 percent reductions in both observed. TUNEL and Annexin-V assays confirmed PAIII cell death to be via apoptosis.

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http://dx.doi.org/10.1080/07357900600629575DOI Listing

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Human PSP94 (prostate secretory protein of 94 amino acids) is a major protein synthesized by the prostate gland and secreted in large quantities in seminal fluid. Previous studies have suggested a potential biomedical utility of PSP94 in applications such as diagnosis/prognosis and in treatment of human prostate cancer (PCa). This study was designed to produce a recombinant human PSP94 (rPSP94) to evaluate its clinical and functional role in PCa.

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We have previously observed that the synthetic peptide corresponding to amino acids 31-45 (PCK3145) of PSP94 can reduce prostate tumor growth in vivo. Moreover, a recently concluded phase IIa clinical trial with patients with hormone refractory prostate cancer indicated that PCK3145 down-regulates the levels of plasma matrix metalloproteinase (MMP)-9, a MMP involved in metastasis and tumor angiogenesis. The purpose of our study was to investigate the molecular mechanisms of action of PCK3145 and whether this peptide could antagonize tumor neovascularization.

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