Notch1 signaling inhibits growth of EC109 esophageal carcinoma cells through downmodulation of HPV18 E6/E7 gene expression.
OBJECTIVE
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 G(2)/M arrest, downmodulation of HPV18 E6/E7 gene expression, and upregulation of p53 expression.


CONCLUSIONS
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.
Zhang
Ke-Jie
KJ
Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Lu
Quan-Yi
QY
Niu
Xiao-Qing
XQ
Zhang
Peng
P
Zhao
Jiang-Ning
JN
Wang
Zhao
Z
Hu
Jia-Sheng
JS
Li
Pu
P
Liu
Wen-Li
WL
D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000235:genetics* / Q000378:metabolism; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; C052603:E6 protein, Human papillomavirus type 18; C052633:E7 protein, Human papillomavirus type 18; C497761:NOTCH1 protein, human; D009856:Oncogene Proteins, Viral; D051881:Receptor, Notch1; D016159:Tumor Suppressor Protein p53