Article
Cell Research (2004) 14, 74–80. doi:10.1038/sj.cr.7290205
Aberrant expression and function of TCF4 in the proliferation of hepatocellular carcinoma cell line BEL-7402
Dong Hong ZHAO1, Jian Jun HONG1, Shi Ying GUO1, Run Lin YANG1, Jun YUAN1, Chuan Jun WEN1, Kai Ya ZHOU1 and Chao Jun LI1
1The Jiangsu Key Laboratory of Molecular Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing 210097, Jiangsu, China.
Correspondence: Chao Jun LI, Tel: 0086 25 3598779, Fax: 0086 25 3598812, E-mail: licj@njnu.edu.cn.
Received 25 December 2003; Revised 10 November 2003; Accepted 16 November 2003.
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
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.
Keywords:
Wnt signaling pathway,
-catenin, dominant negative TCF4
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