Molecular mechanism for androgen-dependent prol : feration and apoptosis of prostatic epithelial cells.

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We hypothesize that androgen responsive element (ARE) decoy can inhibit the proliferation of not only androgen dependent prostatic cancer but also androgen independent one due to androgen receptor (AR) gene mutations. We synthesized a 23-mer ARE decoy and DNA-protein interactions were examined by gel mobility shift assay using nuclear extract prepared from LNCaP cells. Specific binding of ARE decoy to the LNCaP nuclear protein, most likely to be AR, was observed. Next, LNCaP cells were transfected with ARE decoy by lipofection. After 24h incubation, induction of apoptosis was examined by DNA fragmentation. ARE decoy may become a potential therapeutic tool for both androgen dependent and independent prostatic cancers.Mitogen-activated protein kinases (MAPK) function in protein kinase cascades that play critical roles in regulating cell proliferation and differentiation. In vascular smooth muscle cells, α1-adrenergic stimulation increases DNA synthesis and cell proliferation via activation of ERK1/2 MAPK. We examined whether norepinephrine (NE) activates MAPK and stimulates the proliferation of prostatic epithelial and non-epithelial cells. ERK1/2 MAPK was significantly activated by NE (10^<-6> and 10^<-7> M) in stromal cells and smooth muscle cells while not in epithelial cells. JNK and p38 were not activated. The uptake of ^3H-thymidine was significantly increased by NE in both non-epithelial cells, which was inhibited by α1-adrenoceptor. These results suggest that NE may stimulate the proliferation of non-epithelial prostatic cells.