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Carcinogenesis Advance Access originally published online on November 28, 2007
Carcinogenesis 2008 29(2):307-315; doi:10.1093/carcin/bgm269
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© The Author 2007. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Overexpression of cyclin B1 in human esophageal squamous cell carcinoma cells induces tumor cell invasive growth and metastasis

Yongmei Song, Chunling Zhao, Lijia Dong, Ming Fu, Liyan Xue, Zhen Huang, Tong Tong, Zhuan Zhou, Amei Chen, Zhihua Yang, Ning Lu and Qimin Zhan*

State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China

* To whom correspondence should be addressed. Tel: +86 10 67762694; Fax: +86 10 67715058; Email: zhanqimin{at}pumc.edu.cn

Cyclin B1, a key component in the control of cell cycle progression from G2 to M phase, has been implicated in tumorigenesis and the development of malignancy. However, the underlying mechanism by which cyclin B1 acts as an important oncogenic molecule remains largely unknown. Here we show that ectopic expression of cyclin B1 promotes cell proliferation, enhances cell motility and migration and results in increased ability of cells extravasating through the capillary endothelium. Interestingly, isogenic esophageal squamous cell carcinoma (ESCC) cells overexpressing cyclin B1 reveal strong invasive growth and high potential of metastasis to lung in xenograft mice. Suppression of cyclin B1 expression via small interfering RNA approach in high-metastatic esophagus carcinoma cells specifically inhibits their ability to metastasize from the primary ESCC to lung. Notably, altered expression of epithelial markers and mesenchymal markers were observed in the cells overexpressing cyclin B1, suggesting that cyclin B1 contributes to metastasis probably by promoting an epithelial–mesenchymal transition. These results establish a mechanistic link between cyclin B1 and ESCC metastasis and provide novel insight into understanding of cyclin B1 in the development of ESCC malignancy.

Abbreviations: ECEC, esophageal carcinoma endothelium cell; EMT, epithelial–mesenchymal transition; ESCC, esophageal squamous cell carcinoma; HLEC, human lung endothelium cell; MMP, matrix metalloproteinase; NF-{kappa}B, nuclear factor kappa B; PBS, phosphate-buffered saline; TEM, transendothelial migration

Received May 30, 2007; revised October 26, 2007; accepted November 20, 2007.


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