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TCF4在肝癌细胞系BEL-7402增殖中的异常表达及功能

Aberrant expression and function of TCF4 in the proliferation of hepatocellular carcinoma cell line BEL-7402.

作者信息

Zhao Dong Hong, Hong Jian Jun, Guo Shi Ying, Yang Run Lin, Yuan Jun, Wen Chuan Yu, Zhou Kai Ya, Li Chao Jun

机构信息

The Jiangsu Key Laboratory of Molecular Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing 210097, Jiangsu, China.

出版信息

Cell Res. 2004 Feb;14(1):74-80. doi: 10.1038/sj.cr.7290205.

Abstract

Wnt signaling pathway is essential for development and tumorigenesis, however, this signaling pathway in the progress of hepatocellular carcinoma (HCC) remains unclear. In this paper, we studied the function of human T-cell transcription factor-4 (TCF4), a key factor of Wnt signaling pathway, on the proliferation of HCC cell line. We showed that the expression of TCF4 mRNA in HCC cell line BEL-7402 was higher than that in immortalized normal liver cell line L02. Blockage of Wnt pathway by Delta-NTCF4, a dominant negative TCF4, could suppress BEL-7402 cells growth and decrease the expression of cyclin D1 and c-myc, two of target genes of Wnt pathway. On the other hand, stimulating Wnt pathway by introducing a degradation-resistant -catenin S37A could increase BEL-7402 cells proliferation. But all the treatments had no effect on L02 cells. Our data indicated that TCF4 might be another key factor in Wnt pathway involved in HCC cells proliferation and TCF4 could be an effective therapeutic target for suppressing the growth of hepatocellular cancers.

摘要

Wnt信号通路对发育和肿瘤发生至关重要,然而,该信号通路在肝细胞癌(HCC)进展中的作用仍不清楚。在本文中,我们研究了Wnt信号通路的关键因子——人类T细胞转录因子4(TCF4)对肝癌细胞系增殖的作用。我们发现,肝癌细胞系BEL-7402中TCF4 mRNA的表达高于永生化正常肝细胞系L02。显性负性TCF4(Delta-NTCF4)阻断Wnt通路可抑制BEL-7402细胞生长,并降低Wnt通路靶基因之一细胞周期蛋白D1和c-myc的表达。另一方面,通过导入抗降解的β-连环蛋白S37A刺激Wnt通路可增加BEL-7402细胞的增殖。但所有处理对L02细胞均无影响。我们的数据表明,TCF4可能是Wnt通路中另一个参与肝癌细胞增殖的关键因子,并且TCF4可能是抑制肝细胞癌生长的有效治疗靶点。

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