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宫颈上皮内瘤变和宫颈鳞状细胞癌中的凋亡相关蛋白

Apotosis-related proteins in cervical intraepithelial neoplasia and squamous cell carcinoma of the cervix.

作者信息

Cheung Tak-Hong, Chung Tony Kwok-Hung, Lo Keith Wing-Kit, Yu Mei-Yung, Krajewski Stan, Reed John C, Wong Yick-Fu

机构信息

Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong.

出版信息

Gynecol Oncol. 2002 Jul;86(1):14-8. doi: 10.1006/gyno.2002.6655.

DOI:10.1006/gyno.2002.6655
PMID:12079293
Abstract

OBJECTIVES

A loss of balance between proliferation and apoptosis leads to tumor formation. Normal cervical epithelium becomes dysplastic before potentially developing into carcinoma. This study was conducted to delineate the role of apoptosis-related proteins in various stages of development in cervical neoplasia. Both regulator and effector proteins were examined.

METHODS

The expression of apoptosis-related proteins, including five members of the Bcl-2 family and two members of the caspase family, was evaluated in 26 low-grade cervical intraepithelial neoplasias (CIN-L), 37 high-grade cervical intraepithelial neoplasias (CIN-H), and 43 cervical squamous cell carcinomas, using immunohistochemistry. Specimens showing cytosolic immunoreactivity in 10% or more of the neoplastic cells were considered immunopositive.

RESULTS

One hundred six subjects were studied. All seven apoptotic regulators examined were positive in a proportion of these neoplasms. The expression of Caspase 3 was significantly higher in CIN-H than in CIN-L (P = 0.016). The expression of Bak, Caspase 3, and Caspase 6 was reduced in cervical carcinoma compared to CIN-H (P < 0.01, P = 0.026, P < 0.01, respectively).

CONCLUSIONS

There is an increase in expression of Caspase 3 in CIN-H compared to CIN-L and the increase is thought to be related to the increased proliferative activity in dysplastic cells. The reduction of Bax, Caspase 3, and Caspase 6 expression in carcinoma indicates that the apoptotic mechanism has become defective in the process of malignant transformation.

摘要

目的

增殖与凋亡之间的平衡失调会导致肿瘤形成。正常宫颈上皮在可能发展为癌之前会出现发育异常。本研究旨在阐明凋亡相关蛋白在宫颈肿瘤发生发展各阶段中的作用。对调节蛋白和效应蛋白均进行了检测。

方法

采用免疫组织化学方法,评估了26例低级别宫颈上皮内瘤变(CIN-L)、37例高级别宫颈上皮内瘤变(CIN-H)和43例宫颈鳞状细胞癌中凋亡相关蛋白的表达,这些蛋白包括Bcl-2家族的5个成员和caspase家族的2个成员。肿瘤细胞中10%或更多出现胞质免疫反应的标本被视为免疫阳性。

结果

共研究了106名受试者。所检测的所有7种凋亡调节蛋白在部分肿瘤中呈阳性。Caspase 3在CIN-H中的表达显著高于CIN-L(P = 0.016)。与CIN-H相比,宫颈癌中Bak、Caspase 3和Caspase 6的表达降低(分别为P < 0.01、P = 0.026、P < 0.01)。

结论

与CIN-L相比,CIN-H中Caspase 3的表达增加,且这种增加被认为与发育异常细胞中增殖活性的增加有关。癌组织中Bax、Caspase 3和Caspase 6表达的降低表明,在恶性转化过程中凋亡机制已出现缺陷。

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