Expression and Splice Variant Analysis of Human TCF4 Transcription Factor in Esophageal Cancer

人类TCF4转录因子在食管癌中的表达及剪接变异分析

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作者:Gang He, Xingying Guan, Xuedan Chen, Yan Wang, Chao Luo, Bo Zhang

Conclusions

Our data suggested that deregulation of TCF4 isoforms may contribute to the tumorigenesis of ESCC.

Methods

RT-PCR and subsequent cloning and sequencing were applied to identify the splicing isoforms. Western blotting and realtime PCR were used to analyze the expression of TCF4. Knockdown of TCF4 was achieved with siRNA and stable transfection of expression vectors was performed.

Objective

The human T cell transcription factor-4 (TCF4) interacts functionally with β-catenin in the Wnt signaling pathway, whose deregulation is involved in the tumorigenesis of various types of cancers. Recent studies showed that TCF4 mRNAs were subject to alternative splicing, which was proposed to be important in regulating transactivational properties of the corresponding protein isoforms. Here we investigated the splicing isoforms and the roles of TCF4 in human esophageal squamous cell carcinoma.

Results

Our results showed there were a lot of different isoforms of TCF4 mRNA both in human esophageal cancers and cell line. Further, knockdown of TCF4E isoform expression in EC109 cells inhibited the cell growth, while overexpression of TCF4M isoform did not alter its transcription activity. Moreover, sixteen potential binding proteins of TCF4 were preliminarily identified by mass spectrometry. Conclusions: Our data suggested that deregulation of TCF4 isoforms may contribute to the tumorigenesis of ESCC.

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