Abstract
Despite being well recognized as the best biomarker for prostate cancer, pathophysiological roles of prostate-specific antigen (PSA) remain unclear. We report here that tissue PSA may be involved in the hormone-refractory prostate cancer progression. Histological analyses show the increased tissue PSA levels are correlated with lower cell apoptosis index and higher cell proliferation rate in hormone-refractory tumors specimens. By stably transfecting PSA-cDNA into various prostate cancer cell lines, we found PSA could promote the growth of AR-positive CWR22rv1 and high passage LNCaP (hormone refractory prostate cancer cells), but not that of AR-negative PC-3 and Du145 cells. Surprisingly, PSA’s protease activity is not crucial for PSA to stimulate growth and promote AR transactivaton. We further showed that increased PSA could enhance ARA70-induced AR transactivation via modulating p53 pathway that result in the decreased apoptosis and increased cell proliferation in prostate cancer cells. Knockdown of PSA in LNCaP and CWR22rv1 cells causes cell apoptosis and cell growth arrest at the G1 phase.
In vitro
colony formation assay and
in vivo
xenografted tumors results showed the suppression of prostate cancer growth via targeting PSA expression. Collectively, our findings suggest that in addition to be biomarker, PSA may also become a new potential therapeutic target for prostate cancer. PSA-siRNA or smaller molecules that can degrade PSA protein may be developed as alternative approaches to treat the prostate cancer.