Shinmei Shunsuke, Sentani Kazuhiro, Hayashi Tetsutaro, Sakamoto Naoya, Goto Keisuke, Oo Htoo Zarni, Naito Yutaka, Teishima Jun, Matsubara Akio, Oue Naohide, Kuniyasu Hiroki, Yasui Wataru
Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan; Department of Urology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.
Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.
Urol Oncol. 2014 Aug;32(6):769-78. doi: 10.1016/j.urolonc.2014.03.007. Epub 2014 Jun 23.
Although chemotherapy for castration-resistant prostate cancer (CRPC) has been applied clinically in recent years, the effects are not sufficient. It is urgently necessary to develop novel therapeutics for CRPC. We previously generated Escherichia coli ampicillin secretion trap libraries of 2 prostate cancer (PCa) cell lines and normal prostate. By comparing the E. coli ampicillin secretion trap libraries of CRPC cell lines with those of androgen-sensitive PCa cell lines and normal prostate, we focused on the protein-tyrosine-phosphatase of regenerating liver 1 (PRL1) gene and analyzed its expression and biological function.
The expression of PRL1 was examined by quantitative reverse transcription polymerase chain reaction and immunohistochemistry in clinical PCa samples. The effects of PRL1 on PCa cells were evaluated by cell growth, migration, and invasion assays. To investigate the effect of PRL1 on epidermal growth factor receptor (EGFR) signaling, PRL1 knockdown PC3 cells were examined by Western blot and immunohistochemical analyses.
Quantitative reverse transcription polymerase chain reaction revealed that PRL1 was expressed much more highly in PCa than in nonneoplastic prostate samples. High expression of PRL1 detected by immunohistochemistry correlated with poor prognosis after prostatectomy and combined androgen blockade therapy. Functional analysis indicated that PRL1 stimulated cell growth, migration, and invasion in PCa cell lines. Expression EGFR and matrix metalloproteinase 9 was reduced by knockdown of PRL1 in the PC3 cell line.
PRL1 regulates expression of EGFR and modulates downstream targets. PRL1 has potential as a therapeutic target in PCa including CRPC.
尽管近年来去势抵抗性前列腺癌（CRPC）的化疗已在临床上应用，但其效果并不理想。迫切需要开发针对CRPC的新型治疗方法。我们之前构建了2种前列腺癌细胞系和正常前列腺的大肠杆菌氨苄青霉素分泌陷阱文库。通过比较CRPC细胞系与雄激素敏感型前列腺癌细胞系及正常前列腺的大肠杆菌氨苄青霉素分泌陷阱文库，我们聚焦于再生肝1蛋白酪氨酸磷酸酶（PRL1）基因，并分析其表达及生物学功能。
通过定量逆转录聚合酶链反应和免疫组织化学检测临床前列腺癌样本中PRL1的表达。通过细胞生长、迁移和侵袭实验评估PRL1对前列腺癌细胞的影响。为研究PRL1对表皮生长因子受体（EGFR）信号传导的影响，采用蛋白质印迹法和免疫组织化学分析检测PRL1敲低的PC3细胞。
定量逆转录聚合酶链反应显示，PRL1在前列腺癌中的表达远高于非肿瘤性前列腺样本。免疫组织化学检测到的PRL1高表达与前列腺切除术后及联合雄激素阻断治疗后的不良预后相关。功能分析表明，PRL1可促进前列腺癌细胞系的细胞生长、迁移和侵袭。在PC3细胞系中，敲低PRL1可降低EGFR和基质金属蛋白酶9的表达。
PRL1调节EGFR的表达并调节下游靶点。PRL1有潜力成为包括CRPC在内的前列腺癌的治疗靶点。
