PSCA promotes prostate cancer proliferation and cell-cycle progression by up-regulating c-Myc
PSCA promotes prostate cancer proliferation and cell-cycle progression by up-regulating c-Myc
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PSCA 通过上调 c-Myc 促进前列腺癌增殖和细胞周期进展。
DOI：
10.1002/pros.23432
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发表时间：
2017-12-01
期刊：
影响因子：
2.8
通讯作者：
Zhao, Zhigang
中科院分区：
文献类型：
--
作者：
Li, Ermao;Liu, Luhao;Zhao, Zhigang
背景前列腺干细胞抗原（PSCA）是一种糖基化磷脂酰肌醇（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）中的功能和潜在的分子机制仍未完全阐明。本研究旨在探讨PSCA对PCa细胞周期的影响及其机制。方法采用免疫组化、定量逆转录-PCR（qRT-PCR）和Western blotting方法检测PSCA在PCa组织和细胞系中的表达。采用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）的关系。结果免疫组化结果显示PSCA在PCa组织中表达上调，PSCA在PCa组织中表达上调，PSCA在PCa组织中表达上调。PSCA过表达与高Gleason评分（GS）（P=0.028）、阳性BCR（P=0.002）、低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细胞周期进展和肿瘤生长。此外，PI 3 K/AKT信号通路参与PSCA介导的c-Myc表达和细胞增殖。结论PSCA是一种新的细胞周期调控因子，在介导c-Myc诱导的细胞增殖中起关键作用。PSCA可能是前列腺癌患者潜在的诊断标志物和治疗靶点。
BackgroundThe 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.MethodsImmunohistochemistry, 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.ResultsImmunohistochemistry 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.ConclusionsPSCA 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.