Aberrant expression and function of TCF4 in the proliferation of hepatocellular carcinoma cell line BEL-7402
Aberrant expression and function of TCF4 in the proliferation of hepatocellular carcinoma cell line BEL-7402
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DOI：
10.1038/sj.cr.7290205
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发表时间：
2004-02
期刊：
影响因子：
44.1
通讯作者：
Dong-Hong Zhao;Jian-Jun Hong;Shi-ying Guo;R. Yang;Jun Yuan;C. Wen;Kaiying Zhou;Chaoxing Li
中科院分区：
文献类型：
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作者：
Dong-Hong Zhao;Jian-Jun Hong;Shi-ying Guo;R. Yang;Jun Yuan;C. Wen;Kaiying Zhou;Chaoxing Li
Wnt信号通路在肝细胞癌的发生、发展过程中起着重要作用，但该信号通路在肝细胞癌发生、发展过程中的作用尚不清楚。本论文研究了Wnt信号通路的关键因子人T细胞转录因子4（human T-cell transcription factor-4，TCF 4）对肝癌细胞增殖的影响。肝癌细胞系BEL-7402中TCF 4 mRNA的表达高于永生化正常肝细胞系L02。显性负性TCF 4 Δ NTCF 4阻断Wnt通路，可抑制BEL-7402细胞生长，并降低Wnt通路靶基因cyclin D1和c-myc的表达。另一方面，通过引入抗降解的β-catenin S37A来刺激Wnt通路可以增加BEL-7402细胞的增殖。但所有处理对L02细胞均无影响。提示TCF 4可能是Wnt信号通路中参与肝癌细胞增殖的另一个关键因子，TCF 4可能成为抑制肝癌生长的有效治疗靶点。
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 ΔNTCF4, 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 β-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.