Molecular mechanism of human uterine endometrial carcinogenesis

人子宫内膜癌变的分子机制

• 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

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

在正常细胞周期的过程中，必不可少的因素，例如肿瘤抑制基因产物，细胞周期蛋白和CDKS。这些因素的配位异常可能导致细胞的恶性转化。为了检查子宫内膜癌发展的机制，我们研究了子宫内膜癌中这些因素的免疫组织化学反应性。与癌相邻的正常和增生性腹膜阶段显示ER，PR呈阳性染色，但p53为阴性。在59个癌中，有40个对ER和PR表现出强烈的阳性染色，但p53为阴性，而其他19则显示为ER，PR和p53阳性的阴性染色。 p53阳性染色仅位于ER和PR负染色的区域中。在p53染色弱的癌细胞中，RB染色非常阳性，细胞周期蛋白E染色较弱。然而，在p53染色较强的癌细胞中，RB染色要么弱或负，B…更多的UT细胞周期蛋白E染色非常阳性。这些数据表明，似乎存在性别立体受体，肿瘤补充剂和细胞周期蛋白的逐步异常。在正常内膜和子宫内膜癌的增殖阶段观察到CDK4的表达，但是在子宫内膜癌的细胞核中，该表达不是同质的，优选地观察到。在正常内膜的增殖阶段和子宫内膜癌中观察到p16的低表达。 p16表达高表达的区域显示CDK4的低表达，而p16表达低的区域显示了CDK4的高表达。在正常内部测量中没有细胞周期蛋白D1，而在子宫内膜癌的核中观察到高表达，这些癌高度表达CDK4。这些数据表明，人子宫子宫内膜癌存在于p16与CDK4和细胞周期蛋白D1的逆表达。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CDK的逐步异常可能与子宫内膜癌发展中恶性肿瘤的发展相关。较少的

项目成果

Masuzawa,H.,Bodokhon,N-H.,Nakayama,K.,Konishi,I.,Nikaido,T.,and Fujii,S.: "Failure of down-regulation of estrogen receptors and progesterone receptors after medroxyprogesterone acelate administration in endometrial hyperplasias" Cancer.74. 2321-8 (1994)

Masuzawa,H.、Bodokhon,N-H.、Nakayama,K.、Konishi,I.、Nikaido,T. 和 Fujii,S.：“子宫内膜增生症中使用醋酸甲羟孕酮后雌激素受体和孕激素受体下调失败

Oguchi,O.,Mori,A.,Kobayashi,Y.,Horiuchi,A.,Nikaido T.,and Fujii,S.: "Prediction of histopathologic feature and proliferative activity of uterine leiomyoma by magnetic resonance imaging prior to GnRH analogue therapy.-Correlation between T2-weight images a

Oguchi,O.、Mori,A.、Kobayashi,Y.、Horiuchi,A.、Nikaido T. 和 Fujii,S.：“GnRH 类似物治疗前通过磁共振成像预测子宫肌瘤的组织病理学特征和增殖活性

Shuan-fang Li,Tanri Shiozawa,Kuniaki Nakayama,Toshio Nikaido and Shingo Fujii.: "Stepwise Abnormality of Sex Steroid Hormone Receptors,Tumor Suppress Gene Products p53,Rb,and Cyclin E in Human Uterine Endometrial Carcinomas." Cancer. (in press). (1996)

Shuan-fang Li、Tanri Shiozawa、Kuniaki Nakayama、Toshio Nikaido 和 Shingo Fujii.：“人类子宫内膜癌中性类固醇激素受体、肿瘤抑制基因产物 p53、Rb 和细胞周期蛋白 E 的逐步异常。”

Masuzawa, H., Badokhon, N-H., Nakayama, K., Konishi, I., Nikaido, T., and Fujii, S.: "Failure of down-regulation of estrogen receptors and progesterone receptors after medroxyprogesterone acetate administration in endometrial hyperplasias." Cancer.74. 232

Masuzawa, H.、Badokhon, N-H.、Nakayama, K.、Konishi, I.、Nikaido, T. 和 Fujii, S.：“在子宫内膜增生症中给予醋酸甲羟孕酮后雌激素受体和孕激素受体下调失败

Masuzawa,Hideyuki: "Failure of down‐regulation of estrogen receptors and progesterone receptors after medroxyprogesterone acetate administration in endometrial hyperplasias." Cancer. 74. 2321-2328 (1994)

Masuzawa, Hideyuki：“子宫内膜增生症中使用醋酸甲羟孕酮后雌激素受体和孕激素受体下调失败。”74. 2321-2328 (1994)。