Abstract
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.
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Acknowledgements
This project was supported by a grant from the National Natural Science Foundation of China (30570773).
We are grateful to Prof Tom KADESCH (Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA) for providing the pcDNA3.1C-ICN plasmid.
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Zhang, Kj., Lu, Qy., Niu, Xq. et al. Notch1 signaling inhibits growth of EC109 esophageal carcinoma cells through downmodulation of HPV18 E6/E7 gene expression. Acta Pharmacol Sin 30, 153–158 (2009). https://doi.org/10.1038/aps.2008.16
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DOI: https://doi.org/10.1038/aps.2008.16
