Abstract
Recent data suggested that tissue human kallikrein 2 (KLK2) might be involved in the carcinogenesis and tumor metastasis of prostate cancer (PCa). However, the detailed pathophysiological roles of KLK2 in PCa remain unclear. We report here that KLK2 may be treated as a potential therapeutic target in castration-resistant PCa (CRPC). Histologic analyses show that the increased KLK2 expression is correlated with higher cell proliferation rate and lower cell apoptosis index in CRPC specimens. Adding functional KLK2 cDNA into high passage LNCaP cells led to increased cell growth, and knockdown of KLK2 expression with KLK2-siRNA in LNCaP cells resulted in increased cell apoptosis with cell growth arrest at the G1 phase. Results from in vitro colony formation assay and in vivo xenografted PCa tissues also demonstrated that targeting KLK2 led to suppressed growth of PCa in the castration-resistant stage. Further mechanism dissection shows that KLK2 may cooperate with the AR coregulator, ARA70, to enhance AR transactivation that may result in alteration of PCa formation. Together, these results suggested KLK2 might become a new therapeutic target to battle the CRPC and KLK2-siRNA may be developed as an alternative approach to suppress PCa growth.
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Acknowledgments
This work was supported by National Basic Research Program of China (grant no. 2012CB518304); National Institute of Health grants (grant no. CA155477, CA156700); TSTC grant 2012DFG32220; Nature Science Foundation of Tianjin (grant no. 11JCYBJC28400).
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Zhiqun Shang and Yuanjie Niu contributed equally to this work.
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Shang, Z., Niu, Y., Cai, Q. et al. Human kallikrein 2 (KLK2) promotes prostate cancer cell growth via function as a modulator to promote the ARA70-enhanced androgen receptor transactivation. Tumor Biol. 35, 1881–1890 (2014). https://doi.org/10.1007/s13277-013-1253-6
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DOI: https://doi.org/10.1007/s13277-013-1253-6