Li Ermao, Liu Luhao, Li Futian, Luo Lianmin, Zhao Shankun, Wang Jiamin, Kang Ran, Luo Jintai, Zhao Zhigang
Guangdong Provincial Key Laboratory of Urology, Department of Urology and Andrology, Minimally Invasive Surgery Center, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Department of Organ Transplantation, The Section Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Prostate. 2017 Dec;77(16):1563-1572. doi: 10.1002/pros.23432. Epub 2017 Oct 2.
The Prostate stem cell antigen (PSCA) is a glycosylphosphatidylinositol (GPI)-anchored protein. Increasing evidence has indicated PSCA plays an important role in tumorigenesis. However, its function and the underlying molecular mechanisms in prostate cancer (PCa) are still not fully elucidated. In this study, we aimed to explore the effect of PSCA on cell cycle of PCa cells and its mechanism research.
Immunohistochemistry, quantitative reverse transcription-PCR (qRT-PCR) and Western blotting were used to quantify PSCA expression pattern in PCa tissues and cell lines. The association of PSCA expression with the biochemical recurrence (BCR)-free survival and overall survival (OS) of PCa patients were analyzed using Kaplan-Meier method. The roles of PSCA in PCa were confirmed based on both in vitro and in vivo systems.
Immunohistochemistry results showed that PSCA was upregulated in PCa tissue. PSCA overexpression were significantly associated with high Gleason score (GS) (P = 0.028), positive BCR (P = 0.002), and poor OS (P = 0.032) and high c-Myc expression (P = 0.019). PSCA promoted PCa cell cycle progression and tumor growth via increased c-Myc expression. Additional, PI3K/AKT signaling pathways was involved in PSCA-mediated c-Myc expression and cell proliferation.
PSCA is a novel cell cycle regulator with a key role in mediating c-Myc-induced proliferation. PSCA may be a potential diagnostic marker and therapeutic target for patients with PCa.
前列腺干细胞抗原（PSCA）是一种糖基磷脂酰肌醇（GPI）锚定蛋白。越来越多的证据表明PSCA在肿瘤发生中起重要作用。然而，其在前列腺癌（PCa）中的功能及潜在分子机制仍未完全阐明。在本研究中，我们旨在探讨PSCA对PCa细胞细胞周期的影响及其机制研究。
采用免疫组织化学、定量逆转录聚合酶链反应（qRT-PCR）和蛋白质免疫印迹法来定量PSCA在PCa组织和细胞系中的表达模式。使用Kaplan-Meier法分析PSCA表达与PCa患者无生化复发（BCR）生存期和总生存期（OS）的相关性。基于体外和体内系统证实PSCA在PCa中的作用。
免疫组织化学结果显示PSCA在PCa组织中上调。PSCA过表达与高Gleason评分（GS）（P = 0.028）、阳性BCR（P = 0.002）、不良OS（P = 0.032）和高c-Myc表达（P = 0.019）显著相关。PSCA通过增加c-Myc表达促进PCa细胞周期进程和肿瘤生长。此外，PI3K/AKT信号通路参与PSCA介导的c-Myc表达和细胞增殖。
PSCA是一种新型细胞周期调节因子，在介导c-Myc诱导的增殖中起关键作用。PSCA可能是PCa患者潜在的诊断标志物和治疗靶点。
