Seminal Plasma Proteins as Androgen Receptor Coregulators Promote Prostate Cancer Growth
Annual rept. 23 Sep 2013-22 Sep 2014
JOHNS HOPKINS UNIV BALTIMORE MD
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We hypothesized that semenogelins, especially semenogelin I SgI in the presence of zinc, promote prostate cancer growth via functioning as androgen receptor AR coactivators. Using cell lines stably expressing SgI, we investigated biological functions of SgI in prostate cancer. Zinc, without SgI, inhibited cell growth of both AR-positive and AR-negative lines. Co-expression of SgI prevented zinc inhibiting dihydrotestosterone-mediated proliferation of AR-positive cells, whereas SgI andor dihydrotestosterone showed marginal effects in ARnegative cells. Culture in the conditioned medium containing secreted forms of SgI failed to significantly increase cell viability with or without zinc. Similar effects of SgI overexpression in LNCaP on dihydrotestosterone-induced cell invasion, such as its significant enhancement with zinc, were seen. Overexpression of SgI in LNCaP and CWR22Rv1 cells also augmented dihydrotestosterone-mediated prostate-specific antigen mRNA, protein in the presence of zinc. In luciferase assays, SgI showed even slight inhibitory effects at 0 M zinc and significant stimulatory effects at 100 M zinc on dihydrotestosterone-enhanced AR transactivation. Using co-immunoprecipitation, we previously demonstrated dihydrotestosterone-induced physical interactions between AR and SgI. These results suggest that intracellular SgI, together with zinc, functions as an AR coactivator and thereby promotes androgen-mediated prostate cancer progression.
- Medicine and Medical Research