Rb knockdown accelerates bladder cancer progression through E2F3 activation
Rb knockdown accelerates bladder cancer progression through E2F3 activation
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Rb 敲低通过 E2F3 激活加速膀胱癌进展
DOI：
10.3892/ijo.2016.3791
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发表时间：
2017-01-01
影响因子：
5.2
通讯作者：
Zhang, Bo
中科院分区：
文献类型：
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作者：
Wang, Jiang-Ping;Jiao, Yong;Zhang, Bo
膀胱癌是世界上最常见的癌症之一，在受影响的患者中会导致巨大的死亡率和发病率。视网膜母细胞瘤(Rb)蛋白是一种主要的肿瘤抑制因子，控制细胞对潜在致癌刺激的反应。E2F3在不同的人类癌症中总是被干扰，因为它在控制细胞增殖中起着核心作用。在这里，我们研究了Rb是如何通过E2F3和P53调控整合来控制膀胱癌进展的。结果表明，膀胱癌患者Rb表达较低，而E2F3水平较高。Rb基因敲除促进了膀胱肿瘤细胞的增殖和迁移，并随着P53的沉默而加重。有趣的是，Rb沉默导致E2F3、Myc和mTOR信号通路的激活，在体内外主要通过抑制caspase-3而促进膀胱癌细胞的增殖和凋亡。免疫组织化学分析表明，Rb在正常膀胱细胞中高表达，但在膀胱肿瘤组织中完全被抑制，提示Rb可能是一种肿瘤抑制因子。
Bladder cancer is one of the most common cancers diagnosed in the world and leads to significant mortality and morbidity among affected patients. The retinoblastoma (Rb) protein is a main tumor suppressor, controlling cellular responses to potentially oncogenic stimulation. E2F3 was invariably disrupted in different human cancers for its central role in the control of cellular proliferation. Here, we investigated how Rb is integrated to control bladder cancer progression through E2F3 and p53 regulation. The results exhibit that Rb expression is lower in patients with bladder tumor, while E2F3 level is high. Rb knockdown enhanced bladder tumor cell proliferation and migration, aggravated with p53 silence. Interestingly, Rb silence results in E2F3, Myc and mTOR signaling pathway activation, contributing to bladder cancer cell proliferation and apoptosis suppression mainly through caspase-3 inhibition in vitro and in vivo. Immunohistochemical analysis revealed that Rb is highly expressed in normal bladder cells, but was repressed in tumor tissues of the bladder completely, suggesting a possible role of Rb as a tumor suppressor.