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

• Published in: Acta pharmacologica Sinica 2009-02, Vol.30 (2), p.153-158
• Main Authors: Zhang, Ke-jie, Lu, Quan-yi, Niu, Xiao-qing, Zhang, Peng, Zhao, Jiang-ning, Wang, Zhao, Hu, Jia-sheng, Li, Pu, Liu, Wen-li
• Format: Article
• Language: English
• Subjects: Animals; Biomedical and Life Sciences; Biomedicine; Cell cycle; Cell Cycle - physiology; Cell Line, Tumor; Cell proliferation; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Down-Regulation; E7 gene; EC109细胞; esophageal carcinoma; Esophageal Neoplasms - genetics; Esophageal Neoplasms - metabolism; Flow cytometry; Gene expression; Gene Expression Regulation; Human papillomavirus 18; Humans; Immunology; Internal Medicine; Medical Microbiology; Oncogene Proteins, Viral - genetics; Oncogene Proteins, Viral - metabolism; Original; original-article; p53 protein; Pharmacology/Toxicology; Polymerase chain reaction; Receptor, Notch1 - genetics; Receptor, Notch1 - metabolism; Signal transduction; Signal Transduction - physiology; Transfection; Tumor cell lines; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; Vaccine; Western blotting; 基因表达; 生长抑制剂; 食道癌
• ISSN: 1671-4083; 1745-7254
• DOI: 10.1038/aps.2008.16

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.