title: Human kallikrein 2 (KLK2) promotes prostate cancer cell  growth via function as a modulator to promote  the ARA70-enhanced androgen receptor transactivation.
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.
authors.forename: Zhiqun
authors.initials: Z
authors.lastname: Shang
authors.forename: Yuanjie
authors.initials: Y
authors.lastname: Niu
authors.forename: Qiliang
authors.initials: Q
authors.lastname: Cai
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Jing
authors.initials: J
authors.lastname: Tian
authors.forename: Shuyuan
authors.initials: S
authors.lastname: Yeh
authors.forename: Kuo-Pao
authors.initials: KP
authors.lastname: Lai
authors.forename: Chawnshang
authors.initials: C
authors.lastname: Chang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D008807:Mice, Inbred BALB C; D056918:Nuclear Receptor Coactivators / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction; D011944:Receptors, Androgen / Q000378:metabolism*; D020840:Tissue Kallikreins / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection
chemical_list: C111382:NCOA4 protein, human; D056918:Nuclear Receptor Coactivators; D011944:Receptors, Androgen; D020840:Tissue Kallikreins