Wang L, Qin H, Chen B, Xin X, Li J, Han H
Department of Obstetrics and Gynecology, Xijing Hospital, The Fourth Military Medical University, Xi'an, People's Republic of China.
Int J Gynecol Cancer. 2007 Nov-Dec;17(6):1283-92. doi: 10.1111/j.1525-1438.2007.00927.x. Epub 2007 Apr 8.
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.
人宫颈癌是最常见的恶性肿瘤之一，但启动和进展所需的多种致癌损伤的协调机制尚不清楚。Notch信号在维持细胞增殖、分化和凋亡之间的平衡中起关键作用，但Notch信号紊乱可能导致肿瘤发生。我们现在发现，在所有宫颈癌中都能检测到Notch1，包括晚期疾病。我们还在人宫颈癌中组成性过表达活性Notch1，以探讨Notch1信号对人宫颈癌细胞生长的影响，并研究其潜在的分子机制。该信号可能参与人宫颈癌细胞的发育，但过表达的活性Notch1通过诱导细胞周期停滞来抑制其生长。Notch1信号增加通过上调c-Jun抑制激活蛋白（AP）-1活性并降低c-Fos的表达，从而导致人乳头瘤病毒转录下调。因此，Notch1信号起着关键作用并发挥双重效应，以特定于上下文的方式发挥作用。
