We have established a new experimental stromal hyperplasia model corresponding to clinical benign prostatic hyperplasia in terms of the composition of stromal components and functional differentiation of the prostate. Furthermore, the localization and time course of growth factor expression were also similar to those in men with benign prostatic hyperplasia.

Here, we demonstrate that VAT-1 is a novel pathogenic factor in BPH associated with cell proliferation.

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3S2 THE JOURNAL OF UROLOGY®indicates that it may also play roles in regulating smooth muscle cell growth and differentiation. This receptor mediated process has tremendous impact on the function and dysfunction of the prostate. The biological functions and biochemical properties of ala adrenoceptor (AR) in the prostate are not well explored yet. Our study is to utilize adeno-S virus (adS) expression model in human prostate stromal cells (HPS) to delineate alaAR mediated signal transduction pathways.METHODS: Human prostatic stromal cell (HPS) primary cultures infected with adeno-S virus to express either chimeric protein of full length human alaAR and green fluorescent protein (alaAR-GFP) or GFP only, are treated with IO!LM phenylephrine (PE), i!LM doxazosin (DOX), the combination of PE and DOX (PE/DOX) for various times. Extracellular regulated kinase (Erk) activation is assessed by immunoblot using anti-phospho-Erkl and Erk2 antibodies. P38MAPK and SAPK/JNK activations are also explored.RESULTS: HPS cells infected with alaAR-GFP or GFP adS virus at 100 m.o.i. do not display any cytopathic effect or exhibit any morphologic difference compared to the non-infected HPS counterpart. HPS a I aAR chimeric protein expression is evident by flow cytometry, anti-GFP immunoblot, and fluorescent microscopic observation. 30 minutes PE treatment of the cells increases the phospho-Erks (p44 and p42) 6 folds on alaAR-GFP expressing HPS cells compared to that of non-treated counterparts while DOX or PE/DOX has no effect at all. On the other hand, non-infected or GFP virus infected cells show no activation upon PE treatment. These results suggest that PE stimulation activates Erk signal transduction pathways in HPS cells and the activation is alaAR dependant. P38MAPK and SAPK/JNK activation responding to PE stimulation was also observed, however to a lower extent.CONCLUSIONS: Our results illustrate that human prostate stromal cells may respond to a stimulation which activates MAP kinases (Erk) signal transduction pathways. This alaAR mediated activation has been shown to regulate cellular differentiation and proliferation in smooth muscle. In addition, we demonstrate that our HPS and viral transgene model system maybe used to study molecular mechanisms for neurogenic and myogenic regulation in prostate cells. Our findings may provide further insight into the molecular mechanisms of BPH pathogenesis and therapeutic approaches.