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The Transcription Factor FOXA2 Suppresses Gastric Tumorigenesis In Vitro and In Vivo

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Abstract

Background and Aims

The transcription factor forkhead box A2 (FOXA2) plays a central role in the development of endoderm-derived organs. It has been reported that FOXA2 acts as a suppressor in many kinds of tumor. However, little is known about the role of FOXA2 in gastric cancer.

Methods

The expression of FOXA2 in gastric cancer tissue samples from 89 patients was assessed by immunohistochemistry, and the clinicopathological characteristics of the samples were analyzed. The human gastric cancer cell line, BGC-823, was used to investigate the effects of FOXA2 in gastric cancer in vitro and in vivo and the potential mechanism involved was explored.

Results

FOXA2 expression in human gastric cancer cell lines and human gastric cancer tissues was lower compared with the normal gastric epithelium cell line GES1 and normal adult gastric tissues, respectively. Patients with high FOXA2 expression level had longer 5-year overall survival than those with low FOXA2 expression level. FOXA2 markedly inhibited growth of BGC-823 cells accompanied with the cell cycle arrest and apoptosis. Infection of BGC-823 cells by FOXA2 lentivirus resulted in reduced cell tumorigenesis in vitro and in vivo. Moreover, expression of Mucin 5AC was up-regulated along with increased expression of exogenous FOXA2 in BGC-823 cells; in contrast, dedifferentiation markers, BMI, CD54 and CD24, were down-regulated.

Conclusions

These results suggest that FOXA2 induces the differentiation of gastric cancer and highlight FOXA2 as a novel therapeutic target and prognostic marker for human gastric cancer.

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Acknowledgments

This research was sponsored by the China National Key Projects for Infectious Disease (2013ZX10002007-007), the National Natural Science Foundation of China (Key Program 81230011) and the Innovation Program of Shanghai Municipal Education Commission (13ZZ061).

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai, 200003, China

    Chang-Peng Zhu, Jian Wang, Bin Shi, Ping-Fang Hu, Bei-Fang Ning, Qing Zhang, Fei Chen, Xin Zhang & Wei-Fen Xie

  2. Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China

    Wan-Sheng Chen

Authors
  1. Chang-Peng Zhu
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  2. Jian Wang
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  3. Bin Shi
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  4. Ping-Fang Hu
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  5. Bei-Fang Ning
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  6. Qing Zhang
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  7. Fei Chen
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  8. Wan-Sheng Chen
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  9. Xin Zhang
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  10. Wei-Fen Xie
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Corresponding author

Correspondence to Wei-Fen Xie.

Additional information

Chang-Peng Zhu, Jian Wang, and Bin Shi have contributed equally to the work.

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Zhu, CP., Wang, J., Shi, B. et al. The Transcription Factor FOXA2 Suppresses Gastric Tumorigenesis In Vitro and In Vivo. Dig Dis Sci 60, 109–117 (2015). https://doi.org/10.1007/s10620-014-3290-4

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  • DOI: https://doi.org/10.1007/s10620-014-3290-4

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