ATF2预测肾细胞癌预后不良并促进其恶性表型。

ATF2 predicts poor prognosis and promotes malignant phenotypes in renal cell carcinoma.

作者信息

Wu Deng-Shuang, Chen Cheng, Wu Zhen-Jie, Liu Bing, Gao Li, Yang Qing, Chen Wei, Chen Jun-Ming, Bao Yi, Qu Le, Wang Lin-Hui

机构信息

Department of Urology, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai, 200003, China.

Department of Medical Oncology, Jinling Hospital, Nanjing University Clinical School of Medicine, Nanjing, 210002, China.

出版信息

J Exp Clin Cancer Res. 2016 Jul 4;35(1):108. doi: 10.1186/s13046-016-0383-2.

BACKGROUND

Activating transcription factor 2 (ATF2) is a basic helix-loop-helix transcription factor, which has been shown to participate in the pathobiology of numerous cancers. However, the role of ATF2 in renal cell carcinoma (RCC) remains unclear.

METHODS

ATF2 knockdown and overexpression studies were performed in RCC cells to evaluate changes in cell viability, cell cycle, apoptosis, migration and invasion. Xenograft models were used to examine the tumorigenic and metastatic capability of RCC cells upon ATF2 suppression. The expression of ATF2 in human RCC samples was determined using immunohistochemistry on a tissue microarray.

RESULTS

ATF2 knockdown in RCC cells reduced their proliferative and metastatic potentials, whereas ATF2 overexpression enhanced these properties. Mechanistic studies revealed that the transcription of CyclinB1, CyclinD1, Snail and Vimentin was directly regulated by ATF2 in RCC cells. Moreover, ATF2 was shown to be highly expressed in RCC tissues, especially in tumors with metastases. High expression of ATF2 correlated with aggressive clinico-pathological characteristics and predicted poor prognosis of RCC patients.

CONCLUSIONS

ATF2 exerts an oncogenic role in RCC and could serve as an important prognostic biomarker.

背景

活化转录因子2（ATF2）是一种碱性螺旋-环-螺旋转录因子，已被证明参与多种癌症的病理生物学过程。然而，ATF2在肾细胞癌（RCC）中的作用仍不清楚。

方法

在肾癌细胞中进行ATF2敲低和过表达研究，以评估细胞活力、细胞周期、凋亡、迁移和侵袭的变化。使用异种移植模型检测ATF2抑制后肾癌细胞的致瘤和转移能力。通过组织芯片免疫组化法测定人肾细胞癌样本中ATF2的表达。

结果

肾癌细胞中ATF2敲低降低了其增殖和转移潜能，而ATF2过表达增强了这些特性。机制研究表明，肾癌细胞中细胞周期蛋白B1（CyclinB1）、细胞周期蛋白D1（CyclinD1）、蜗牛蛋白（Snail）和波形蛋白（Vimentin）的转录直接受ATF2调控。此外，ATF2在肾癌细胞组织中高表达，尤其是在有转移的肿瘤中。ATF2的高表达与侵袭性临床病理特征相关，并预示肾细胞癌患者预后不良。