Overexpressed active Notch1 induces cell growth arrest of HeLa cervical carcinoma cells.
Human cervical carcinoma is one of the most common malignant tumors, but the mechanisms that orchestrate the multiple oncogenic insults required for initiation and progression are not clear. Notch signaling plays a critical role in maintaining the balance between cell proliferation, differentiation, and apoptosis, but perturbed Notch signaling may contribute to tumorigenesis. We now show that Notch1 is detected in all cervical cancer, including advanced diseases. We also constitutively overexpressed active Notch1 in human cervical carcinoma to explore the effects of Notch1 signaling on human cervical carcinoma cell growth and to investigate the underlying molecular mechanisms. The signaling may participate in the development of human cervical carcinoma cells, but overexpressed active Notch1 inhibits their growth through induction of cell cycle arrest. Increased Notch1 signaling induced a downmodulation of human papillomavirus transcription through suppression of activator protein (AP)-1 activity by upregulation of c-Jun and the decreased expression of c-Fos. Thus, Notch1 signaling plays a key role and exerts dual effects, functioning in context-specific manner.
Wang
L
L
Department of Obstetrics and Gynecology, Xijing Hospital, The Fourth Military Medical University, Xi'an, People's Republic of China. wanglin1@fmmu.edu.cn
Qin
H
H
Chen
B
B
Xin
X
X
Li
J
J
Han
H
H
D017209:Apoptosis / Q000502:physiology; D002277:Carcinoma / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D019925:Cyclin A / Q000378:metabolism; D056750:Cyclin A1; D019927:Cyclin E / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D051881:Receptor, Notch1 / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D018808:Transcription Factor AP-1 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000378:metabolism*
C503745:CCNA1 protein, human; D019925:Cyclin A; D056750:Cyclin A1; D019927:Cyclin E; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; D016160:Retinoblastoma Protein; D018808:Transcription Factor AP-1; D016159:Tumor Suppressor Protein p53