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Updated: Apr 16, 2026

Development of Compendium for Esophageal Squamous Cell Carcinoma
Published on: April 12, 2024
Expression and Splice Variant Analysis of Human TCF4 Transcription Factor in Esophageal Cancer
Gang He1, Xingying Guan1, Xuedan Chen1
1Department of Medical Genetics, Third Military Medical University, Chongqing 400038, China.
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.
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.
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.
Insights
Deregulation of TCF4 splicing isoforms contributes to esophageal squamous cell carcinoma (ESCC) tumorigenesis. Specific isoforms impact cell growth, suggesting TCF4
Area of Science:
- Molecular Biology
- Cancer Research
- Genetics
Background:
- The TCF4 transcription factor interacts with β-catenin in Wnt signaling, a pathway implicated in cancer.
- TCF4 mRNA undergoes alternative splicing, potentially regulating protein isoform function.
- TCF4's role in esophageal squamous cell carcinoma (ESCC) requires further investigation.
Purpose of the Study:
- To investigate TCF4 splicing isoforms in human ESCC.
- To determine the functional roles of TCF4 isoforms in ESCC cell lines.
- To identify potential TCF4 binding proteins.
Main Methods:
- RT-PCR, cloning, and sequencing to identify TCF4 splicing isoforms.
- Western blotting and real-time PCR to analyze TCF4 expression.
- siRNA-mediated knockdown and expression vector transfection to study TCF4 function.
- Mass spectrometry for preliminary identification of TCF4 binding proteins.
Main Results:
- Numerous TCF4 mRNA isoforms were identified in ESCC tissues and cell lines.
- Knockdown of the TCF4E isoform inhibited cell growth in EC109 cells.
- Overexpression of the TCF4M isoform did not affect transcription activity.
- Sixteen potential TCF4 binding proteins were preliminarily identified.
Conclusions:
- Deregulation of TCF4 isoforms may contribute to ESCC tumorigenesis.
- Specific TCF4 isoforms play distinct roles in ESCC development.
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