Acta Pharmacologica Sinica (2009) 30: 153-158; doi: 10.1038/aps.2008.16

Acta Pharmacologica Sinica (2009) 30: 153-158; doi: 10.1038/aps.2008.16; published online 5th January 2009

Original Article

Notch1 signaling inhibits growth of EC109 esophageal carcinoma cells through downmodulation of HPV18 E6/E7 gene expression

Ke-jie ZHANG^1,2, Quan-yi LU², Xiao-qing NIU², Peng ZHANG², Jiang-ning ZHAO², Zhao WANG², Jia-sheng HU², Pu LI², Wen-li LIU^1,*

¹Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; ²Department of Hematology, Zhongshan Hospital, Xiamen University, Fujian Medical University Clinic Teaching Hospital, Xiamen 361004, China

Aim: To investigate the role of the Notch1 signaling pathway in growth arrest of an esophageal carcinoma cell line (EC109) in vitro and the mechanism involved.

Methods: An intracellular domain of Notch1 (ICN) was transfected into cultured EC109 cells by lipofectamine transfection. Subsequently, the proliferation of the transfected cells was measured by an MTT assay. Cell cycle distribution was analyzed by flow cytometry. Human papillomavirus type 18 (HPV18) E6/E7 mRNA expression was detected by RT-PCR, and p53 protein expression was detected by Western blot.

Results: Activation of Notch1 signaling resulted in inhibition of EC109 cell proliferation with the induction of G₂/M arrest, downmodulation of HPV18 E6/E7 gene expression, and upregulation of p53 expression.

Conclusion: Repression of HPV18 E6/E7 expression by Notch1 signaling results in the activation of p53-mediated pathways with concomitant growth suppression of HPV18-positive EC109 cells.

Keywords: Notch1; esophageal carcinoma; EC109 cell line; growth inhibition; HPV18 E6/E7; p53

This project was supported by a grant from the National Natural Science Foundation of China (30570773).

* Correspondence to Prof Wen-li LIU.
E-mail liuwenli1945@sina.com
Received 2008-10-04 Accepted 2008-11-18

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