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


CONCLUSIONS
LCN2 could facilitate cell proliferation of CRPC via AR transcriptional activity. LCN2 could be a novel target in CRPC.
Department of Urology, Huashan Hospital, Fudan University, Shanghai, China.
Guanxiong
G
Ding
Department of Urology, Huashan Hospital, Fudan University, Shanghai, China.
Jianqing
J
Wang
Department of Urology, Huashan Hospital, Fudan University, Shanghai, China.
Chenchen
C
Feng
Department of Urology, Huashan Hospital, Fudan University, Shanghai, China.
Haowen
H
Jiang
Department of Urology, Huashan Hospital, Fudan University, Shanghai, China.|Department of Urology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
Jianfeng
J
Xu
Department of Urology, Huashan Hospital, Fudan University, Shanghai, China.
Qiang
Q
Ding
D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000071068:Lipocalin-2 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D009004:Monosaccharide Transport Proteins; D064129:Prostatic Neoplasms, Castration-Resistant / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D034622:RNA Interference; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D047368:Tumor Burden; D015854:Up-Regulation
C410798:AR protein, human; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D026901:Membrane Transport Proteins; D009004:Monosaccharide Transport Proteins; D011944:Receptors, Androgen; C551031:SLC45a3 protein, human
androgen receptor; castration-resistant prostate cancer; cell proliferation; lipocalin 2; transcriptional activity