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Molecular mechanism of human uterine endometrial carcinogenesis

人子宫内膜癌变的分子机制

基本信息

批准号：
06454468
负责人：
NIKAIDO Toshio
金额：
$ 4.1万
依托单位：
Shinshu University School Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06454468/
关键词：
Gynecological tumor Endometrial carcinoma Tumor suppressor gene Cell cycle regulator Cyclin Cdc2 family cdc2ファミリー

项目摘要

In the process of normal cell cycle, the cooperation of factors such as tumor suppressor gene products, cyclins, and cdks is essential. Abnormalities of the cooperation of these factors may result in malignant transformation of the cell. To examine the mechanism in the development of the endometrial carcinomas, we studied the immunohistochemical reactivity of these factors in endometrial carcinoma. The normal and hyperplastic endometria adjacent to carcinoma showed positive staining for ER,PR,but negative for p53. Of 59 carcinomas, 40 showed strongly positive staining for ER and PR,but negative for p53, while the other 19 showed negative staining for ER,PR,and positive for p53. The p53 positive staining was located just in the areas with negative staining for ER and PR.In the cancer cells with weak p53 staining, Rb staining were strongly positive and cyclin E staining were weakly positive. However, in the cancer cells with strong p53 staining, Rb staining was either weak or negative, b … More ut cyclin E staining was strongly positive. These data suggest that a stepwise abnormalities of sex steroid receptors, tumor suppressors, and cyclins seems to exist. The expression of cdk4 was observed in the proliferative phase of normal endometria as well as endometrial carcinomas, but the expression was not homogenous and preferentially observed in the nucleus of the endometrial carcinomas. Low expression of p16 was observed in the proliferative phase of normal endometria and in the endometrial carcinomas. The area with high expression of p16 showed low expression of cdk4, while the area with low expression of p16 showed high expression of cdk4. No cyclin D1 expressed in normal endometria, while high expression was observed in the nucleus of the endometrial carcinomas which are highly expressed of cdk4. These data suggest that inverse expression of p16 versus cdk4 and cyclin D1 is present in the human uterine endometrial carcinomas. Taken together, , our data suggest that a stepwise abnormalities of the tumor suppressor gene products, cyclins, and cdks may correlate with the advancement of malignancy in the development of the endometrial carcinoma. Less

在正常的细胞周期过程中，肿瘤抑制基因产物、细胞周期蛋白、cdks等因子的协同作用是必不可少的。这些因素合作的异常可能导致细胞的恶性转化。为了探讨子宫内膜癌的发生机制，我们研究了这些因子在子宫内膜癌中的免疫组织化学反应性。正常及癌旁增生子宫内膜ER、PR染色阳性，p53染色阴性。59例癌中，ER、PR强阳性40例，p53阴性，ER、PR阴性19例，p53阳性。p53阳性染色仅位于ER和pr阴性染色区，p53弱染色的癌细胞Rb强阳性，cyclin E弱阳性。而在p53染色较强的癌细胞中，Rb染色呈弱或阴性，而cyclin E染色呈强阳性。这些数据表明，性类固醇受体、肿瘤抑制因子和细胞周期蛋白的逐渐异常似乎存在。cdk4在正常子宫内膜和子宫内膜癌的增殖期均有表达，但表达不均匀，在子宫内膜癌的细胞核中优先表达。p16在正常子宫内膜增殖期和子宫内膜癌中均有低表达。p16高表达区cdk4低表达，p16低表达区cdk4高表达。正常子宫内膜未见cyclin D1表达，而cdk4高表达的子宫内膜癌细胞核中cyclin D1高表达。这些数据表明p16对cdk4和细胞周期蛋白D1的逆表达存在于人子宫内膜癌中。综上所述，我们的数据表明，肿瘤抑制基因产物、细胞周期蛋白和cdks的逐步异常可能与子宫内膜癌的恶性进展有关。少