AIB1 predicts bladder cancer outcome and promotes bladder cancer cell proliferation through AKT and E2F1.

AIB1 predicts bladder cancer outcome and promotes bladder cancer cell proliferation through AKT and E2F1.
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AIB1 通过 AKT 和 E2F1 预测膀胱癌结果并促进膀胱癌细胞增殖

DOI:
10.1038/bjc.2013.81
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发表时间:
2013-04-16
影响因子:
8.8
通讯作者:
Luo, J-H
Luo, J-H
中科院分区:
医学1区
文献类型:
--
作者:
Tong, Z-T;Wei, J-H;Zhang, J-X;Liang, C-Z;Liao, B.;Lu, J.;Fan, S.;Chen, Z-H;Zhang, F.;Ma, H-H;Qian, W-C;Kong, L-L;Fang, Y.;Chen, W.;Xie, D.;Luo, J-H

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背景:我们先前证明AIB1过表达是膀胱癌(BC)患者生存期缩短的独立分子标志物。在这项研究中,我们的特点AIB1在BC tumorigenicity.Methods的作用和分子机制:AIB1的表达测定在非肌肉浸润性BC组织和相邻的正常膀胱组织的免疫组化。此外,AIB1的致瘤性进行了评估,在体外和体内的功能assessment.Results:AIB1的过表达,观察组织中的46个146例非肌肉浸润性BC和是一个独立的预测不良无进展生存。慢病毒介导的AIB1敲低抑制体外和体内细胞增殖,而AIB1过表达促进体外细胞增殖。AIB1基因敲除可通过AKT通路和E2F1抑制细胞周期关键蛋白的表达,从而导致细胞周期阻滞于G1期。结论:AIB1基因敲除可通过AKT通路和E2F1促进BC细胞的增殖。此外,AIB1过表达可预测非肌肉浸润性BC患者的肿瘤进展。
Background:We previously demonstrated that AIB1 overexpression is an independent molecular marker for shortened survival of bladder cancer (BC) patients. In this study, we characterised the role and molecular mechanisms of AIB1 in BC tumorigenicity.Methods:AIB1 expression was measured by immunohistochemistry in non-muscle-invasive BC tissue and adjacent normal bladder tissue. In addition, the tumorigenicity of AIB1 was assessed with in vitro and in vivo functional assays.Results:Overexpression of AIB1 was observed in tissues from 46 out of 146 patients with non-muscle-invasive BC and was an independent predictor for poor progression-free survival. Lentivirus-mediated AIB1 knockdown inhibited cell proliferation both in vitro and in vivo, whereas AIB1 overexpression promoted cell proliferation in vitro. The growth-inhibitory effect induced by AIB1 knockdown was mediated by G1 arrest, which was caused by reduced expression of key cell-cycle regulatory proteins through the AKT pathway and E2F1.Conclusion:Our results suggest that AIB1 promotes BC cell proliferation through the AKT pathway and E2F1. Furthermore, AIB1 overexpression predicts tumour progression in patients with non-muscle-invasive BC.
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