Expression of nuclear Notch3 in cervical squamous cell carcinomas and its association with adverse clinical outcomes
Expression of nuclear Notch3 in cervical squamous cell carcinomas and its association with adverse clinical outcomes
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DOI：
10.1016/j.ygyno.2010.03.004
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发表时间：
2010-06-01
影响因子：
4.7
通讯作者：
Miyazaki, Kohji
中科院分区：
文献类型：
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作者：
Yeasmin, Shamima;Nakayama, Kentaro;Miyazaki, Kohji
目标。本研究的目的是阐明Notch3在人宫颈癌中的功能作用。应用免疫组织化学方法评估Notch3在宫颈癌中的表达，采用回顾性图表法收集临床变量数据。我们采用双色荧光原位杂交（FISH）技术分析宫颈癌DNA拷贝数的变化。利用γ -分泌酶抑制剂和Notch3特异性SiRNA对Notch3基因进行失活和敲低，以评估Notch3在宫颈癌中的体内和体外功能。免疫组化分析显示，Notch3在宫颈鳞状细胞癌中较腺癌明显过表达。与正常宫颈组织和宫颈上皮内肿瘤（CINs）相比，鳞状细胞癌表现出更高的核Notch3免疫反应性。FISH分析未发现宫颈癌中Notch3扩增。Notch3核表达与推测的Notch3配体jagded -1和潜在的Notch3下游靶点Pbx1b显著相关(P
Objective. The aim of this study was to clarify the functional role of Notch3 in human cervical carcinomas.Methods. Notch3 expression in cervical cancer was assessed by immunohistochemistry, and data on clinical variables were collected by retrospective chart review. We used dual-color fluorescence in situ hybridization (FISH) to analyze DNA copy number alterations in cervical cancer. Inactivation of Notch3 and knocking down Notch3 gene were done using gamma-secretase inhibitor and Notch 3 specific SiRNA to asses Notch3 function in cervical cancer either in vivo or in vitro.Results. Immunohistochemical analysis revealed that Notch3 was significantly overexpressed in cervical squamous cell carcinomas compared with adenocarcinomas. In contrast to normal cervical tissue and cervical intraepithelial neoplasms [CINs], squamous cell carcinomas demonstrated higher nuclear Notch3 immunoreactivity. Notch3 amplification was not found in any cervical carcinomas using FISH analysis. Notch3 nuclear expression was significantly correlated with Jagged-1, a putative Notch3 ligand, and Pbx1b, a potential Notch3 downstream target (P