Lipocalin 2 over-expression facilitates progress of castration-resistant prostate cancer via improving androgen receptor transcriptional activity

// Guanxiong Ding 1, * , Jianqing Wang 1, * , Chenchen Feng 1 , Haowen Jiang 1 , Jianfeng Xu 1, 2 , Qiang Ding 1 1 Department of Urology, Huashan Hospital, Fudan University, Shanghai, China 2 Department of Urology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA * These authors have contributed equally to this work Correspondence to: Jianfeng Xu, email: drwang_shan@126.com Qiang Ding, email: dingqiang888@126.com Keywords: castration-resistant prostate cancer, lipocalin 2, androgen receptor, cell proliferation, transcriptional activity Received: April 25, 2016 Accepted: August 13, 2016 Published: September 01, 2016 ABSTRACT Background: Castration-resistant prostate cancer (CRPC) is the lethal phenotype of prostate cancer. Lipocalin 2 (LCN2) is aberrantly expressed in many cancers including primary prostate cancer (PCa), but its role in CRPC has not been reported. Results: LCN2 expression was upregulated in human primary PCa and CRPC tissues. Overexpression of LCN2 promoted C4-2B and 22RV1 cell proliferation while knockdown of LCN2 markedly inhibited C4-2B and 22RV1 cell growth. LCN2 overexpression led to increased AR downstream gene SLC45A3 without upregulating AR expression. In the xenograft model, overexpression of LCN2 significantly promoted tumor growth. Methods: LCN2 expression was detected in primary PCa and CRPC tissues and cell lines C4-2B and 22RV1 using immunohistochemistry and western blotting, respectively. Serum LCN2 level was detected vi ELISA. Lentiviruses-mediated over-expression of LCN2 and LCN2 knockdown were performed in CRPC cell lines. Expressions of androgen receptor (AR) downstream genes was examined in cell lines, in CRPC tissues, and in animal models. Conclusion: LCN2 could facilitate cell proliferation of CRPC via AR transcriptional activity. LCN2 could be a novel target in CRPC.