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

Guanxiong Ding,Chenchen Feng,Jianqing Wang,Haowen Jiang,Qiang Ding,Jianfeng Xu

doi:10.18632/oncotarget.11790

Abstract

BackgroundCastration-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.ResultsLCN2 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.MethodsLCN2 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.ConclusionLCN2 could facilitate cell proliferation of CRPC via AR transcriptional activity. LCN2 could be a novel target in CRPC.

Highlights

Among all genitourinary cancers, lethal or high risk prostate cancer (PCa) is still a major cause of cancer-related death
Lipocalin 2 (LCN2) expression was upregulated in human primary PCa and Castration-resistant prostate cancer (CRPC) tissues
As we have previously shown that PCa expressed higher LCN2, we have in the current study investigated whether LCN2 was further upregulated in CRPC

Summary

Introduction

Lethal or high risk PCa is still a major cause of cancer-related death. Lethal PCa, in most case at its castration-resistant stage, confers a poor prognosis and definitive therapy with durable effect is lacking. Several decades ago, when prostate cancer was introduced as an androgen-dependent disease, the treatment has been changed considerably [1]. Androgen deprivation therapy (ADT), as a standard care currently, is typically used through surgical castration or LHRH agonists/antagonists, when radiotherapy or surgery is failed. Despite the initial benefit upon the ADT, CRPC, which is known as hormone-refractory prostate cancer (HRPC) in the past, may be evolved from primary PCa 12-48 months following treatment [2, 3]. Regardless of whether testosterone reached castration level, the definition of CRPC is based on disease progression. 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

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Conclusion