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Overexpression of EB1 in human esophageal squamous cell carcinoma (ESCC) may promote cellular growth by activating β-catenin/TCF pathway

Oncogene volume 24, pages 6637–6645 (2005)Cite this article

Abstract

Esophageal squamous cell carcinoma (ESCC) has a multifactorial etiology involving environmental and/or genetic factors. End-binding protein 1 (EB1), which was cloned as an interacting partner of the adenomatous polyposis coli (APC) tumor suppressor protein, was previously found overexpressed in ESCC. However, the precise role of EB1 in the development of this malignancy has not yet been elucidated. In this study, we analysed freshly resected ESCC specimens and demonstrated that EB1 was overexpressed in approximately 63% of tumor samples compared to matched normal tissue. We report that overexpression of EB1 in the ESCC line EC9706 significantly promotes cell growth, whereas suppression of EB1 protein level by RNA interference significantly inhibited growth of esophageal tumor cells. In addition, EB1 overexpression induced nuclear accumulation of β-catenin and promoted the transcriptional activity of β-catenin/T-cell factor (TCF). These effects were partially or completely abolished by coexpression of APC or ΔN TCF4, respectively. Also, we found that EB1 affected the interaction between β-catenin and APC. Furthermore, EB1 overexpression was correlated with cytoplasmic/nuclear accumulation of β-catenin in primary human ESCC. Taken together, these results support the novel hypothesis that EB1 overexpression may play a role in the development of ESCC by affecting APC function and activating the β-catenin/TCF pathway.

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Abbreviations

ESCC:

esophageal squamous cell carcinoma

APC:

adenomatous polyposis coli

TCF:

T-cell factor

EC:

esophageal cancer

GSK 3β:

glycogen synthesis kinase 3β

LEF:

leukemia enhancing factor

RT–PCR:

reverse transcription–polymerase chain reaction

TK:

thymidine kinase

HEK:

human embryonal kidney

CGH:

comparative genomic hybridization

NLS:

nuclear localization signals

NES:

nuclear export signals

M-MLV:

mouse-mammary tumor virus

HA:

hemagglutinin

PBS:

phosphate buffered saline

BSA:

bovine serum albumin

IP:

immunoprecipitation

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Acknowledgements

We thank Professor Karl Munger for his constructive suggestions and generous help in preparation of the manuscript; Professor B Vogelstein for the APC expression plasmid; Professor ER Fearon for ΔN TCF4 and Professor Mingrong Wang for EC9706 cells. This work was supported by National Natural Science Foundation (39925020, 30271451) and National Basic Research Program (G1998051204, 2004CB518701), PR China.

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Author notes

  1. Xiaobo Zhou

    Present address: Department of Pathology, Harvard Medical School, Boston, USA

  2. Yihua Wang and Xiaobo Zhou: These authors contributed equally to this work

Authors and Affiliations

  1. Laboratory of Cell and Molecular Biology, Cancer Institute & Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100021, PR China

    Yihua Wang, Xiaobo Zhou, Hongxia Zhu, Shuang Liu, Cuiqi Zhou, Guo Zhang, Lanping Quan, Jinfeng Bai & Ningzhi Xu

  2. Department of Pathology, Cancer Institute & Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, PR China

    Liyan Xue & Ning Lu

  3. National Laboratory of Molecular Oncology, Cancer Institute & Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, PR China

    Qimin Zhan

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  1. Yihua Wang
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Wang, Y., Zhou, X., Zhu, H. et al. Overexpression of EB1 in human esophageal squamous cell carcinoma (ESCC) may promote cellular growth by activating β-catenin/TCF pathway. Oncogene 24, 6637–6645 (2005). https://doi.org/10.1038/sj.onc.1208819

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