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下调人膀胱癌中 ErbB3 结合蛋白 1 的表达促进肿瘤进展和细胞增殖。

Down-regulation of the ErbB3 binding protein 1 in human bladder cancer promotes tumor progression and cell proliferation.

机构信息

Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180, China.

出版信息

Mol Biol Rep. 2013 May;40(5):3799-805. doi: 10.1007/s11033-012-2458-2. Epub 2013 Jan 3.

Abstract

The ErbB3 binding protein 1 (Ebp1) represents a downstream effector of the ErbB signaling network and has been demonstrated to be a potent tumor suppressor in various human malignancies, however, its involvement in human bladder cancer is still unclear.To investigate the clinical significance and potential role of ErbB3 binding protein 1 (Ebp1) in bladder cancer. Ebp1 expression at protein and gene levels in 52 surgically removed bladder cancer specimens as well as 21 adjacent normal bladder specimens were respectively detected by immunohistochemistry and qRT-PCR. The association of Ebp1 protein expression with the clinicopathological features of bladder cancer was also statistically analyzed. Its roles in bladder cancer cell line were further evaluated. The expression level of Ebp1 protein and gene in bladder cancer tissues was significantly lower than that in adjacent normal bladder tissues (P < 0.01). When categorized into low vs. high expression, the down-regulation of Ebp1 protein was associated with the advanced pathologic stage (P = 0.036) and the high histologic grade (P = 0.001) of patients with bladder cancer. Moreover, following the transfection of Ebp1 in bladder cancer cells, not only cell proliferation and cell invasion decreased significantly, but also the cell cycle was blocked at G0/G1 stage. Our data suggest for the first time that the down-regulation of Ebp1 closely correlates with advanced clinicopathological characteristics of human bladder cancer. Furthermore, Ebp1 plays an important role in the bladder cancer cells' proliferation by regulating the cancer cell cycle from G0/G1 to S.

摘要

erbB3 结合蛋白 1(Ebp1)是 erbB 信号网络的下游效应物,已被证明在多种人类恶性肿瘤中是一种有效的肿瘤抑制因子,然而,其在人类膀胱癌中的作用尚不清楚。为了研究 erbB3 结合蛋白 1(Ebp1)在膀胱癌中的临床意义和潜在作用。通过免疫组织化学和 qRT-PCR 分别检测了 52 例手术切除的膀胱癌标本和 21 例相邻正常膀胱标本中 Ebp1 的蛋白和基因水平表达。还统计分析了 Ebp1 蛋白表达与膀胱癌临床病理特征的相关性。进一步评估了其在膀胱癌细胞系中的作用。膀胱癌组织中 Ebp1 蛋白和基因的表达水平明显低于相邻正常膀胱组织(P < 0.01)。当分为低表达与高表达时,Ebp1 蛋白的下调与膀胱癌患者的晚期病理分期(P = 0.036)和高组织学分级(P = 0.001)相关。此外,在膀胱癌细胞中转染 Ebp1 后,不仅细胞增殖和细胞侵袭明显降低,而且细胞周期被阻滞在 G0/G1 期。我们的数据首次表明,Ebp1 的下调与人类膀胱癌的晚期临床病理特征密切相关。此外,Ebp1 通过调节癌细胞从 G0/G1 期到 S 期的周期,在膀胱癌细胞的增殖中发挥重要作用。

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