Involvement of the abnormality of cyclins, cyclin-dependent kinases or tumor suppressor gene products in the acquisition of the malignant potential of the endometrial carcinomas.

细胞周期蛋白、细胞周期蛋白依赖性激酶或抑癌基因产物的异常参与子宫内膜癌恶性潜能的获得。

• 批准号: 09470355
• 负责人: NIKAIDO Toshio
• 金额: $ 9.15万
• 依托单位: Shinshu University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09470355/
• 关键词: cell cycle; cyclins; cyclin-dependent kinases (cdks); tumor suppressor gene; endometrial carcinomas; プロモーター; ER; PR; サイクリンA; p53; サイクリン; 免疫組織染色; RB

Interactions of cyclins, cyclin-dependent kinases (cdks) and tumor suppressor gene products are essential in cell cycle progression, and deranged expression of these factors are reported to evoke malignant transformation of the cell. To elucidate the tumorigenetic process of the endometrial carcinomas, expression of the cell cycle related molecules in normal and malignant endometrial tissues was investigated by immunostaining. In the normal endometrium, expression of cyclin A, cyclin B1, cyclin E, cdc2, cdk2 and p16 was sporadically observed in the glandular epithelia of the proliferative phase. In 64 cases of endometrial carcinomas, the number of positive cases for cyclin A, cyclin B1, cyclin D1, cyclin E, cdc2, cdk2, cdk4, p53, P16 and RB was 11, 32, 22, 41, 43, 32, 8, 22, 39, and 32 cases, respectively. The topographical distribution of cyclin D1, cyclin A and p53 positive cells correlated each other. Above 64 cases were classified into two groups. The first group was consisted of the cases showing positive for only cyclin E, and the second group was consisted of those expressing cyclin D1, p53 and cyclin A. The first group tended to contain well differentiated cases, and poorly differentiated cases were more frequently found in the second group. These findings suggest that accumulations of abnormalities of the cell cycle related factors are involved in the acquisition of the malignant potential of the endometrial carcinomas.

细胞周期蛋白、细胞周期蛋白依赖性激酶（cdks）和肿瘤抑制基因产物的相互作用在细胞周期进程中是必不可少的，据报道这些因子的紊乱表达会引起细胞的恶性转化。为探讨子宫内膜癌的发生发展过程，采用免疫组化方法检测了正常和恶性子宫内膜组织中细胞周期相关分子的表达。在正常子宫内膜中，cyclin A、cyclin B1、cyclin E、cdc2、cdk2和p16在增殖期腺上皮中零星表达。64例子宫内膜癌中cyclin A、cyclin B1、cyclin D1、cyclin E、cdc2、cdk2、cdk4、p53、P16和RB的阳性表达分别为11、32、22、41、43、32、8、22、39和32例。cyclin D1、cyclin A和p53阳性细胞的局部分布具有相关性。以上64例患者分为两组。第一组为仅表达cyclin E的病例，第二组为表达cyclin D1、p53和cyclin A的病例。第一组倾向于包含高分化的病例，而低分化的病例在第二组中更常见。这些结果表明，细胞周期相关因子异常的积累参与了子宫内膜癌恶性潜能的获得。

项目成果

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Kawa,S.et al：“在胰腺癌细胞系的生长抑制过程中，维生素 D 类似物上调 p21 和 p27。”

Kusama, H., Nikaido, T. et al.: "Tranilast may prevent restenosis after percutaneous transluminal coronary angioplasty(PTCA) though the activation of the p21 wafl and p53."Atherosclerosis. 143. 307-313 (1999)

Kusama, H., Nikaido, T. 等人：“曲尼司特可以通过激活 p21 wafl 和 p53 来预防经皮冠状动脉成形术 (PTCA) 后的再狭窄。”动脉粥样硬化。

Horiuchi, A., Nikaido, T., Zhai, Y-L., Ito, K., Orii, A., and Fujii, S.: "Heparin inhibits proliferation and induces a-smooth muscle Actin expression in human myometrium and leiomyomas, in vitro."MolHum Reprod. 5. 139-45 (1999)

Horiuchi, A.、Nikaido, T.、Zhai, Y-L.、Ito, K.、Orii, A. 和 Fujii, S.：“肝素抑制增殖并诱导人子宫肌层和平滑肌瘤中的 α-平滑肌肌动蛋白表达，

Lu, X., Nikaido, T. et al.: "Abnormal expression of sex steroid receptors, and cell cycle-related molecules in adenocarcinoma in situ of the uterine cervix."Int J Gynecol Pathol. 18. 109-114 (1999)

Lu, X., Nikaido, T. 等人：“子宫颈原位腺癌中性类固醇受体和细胞周期相关分子的异常表达。”Int J Gynecol Pathol。

Kuroiwa S.et al: "Aberrant expression of cell cycle-related genes in dying cells retinal ischemic injury." Invest Ophth Vis Sci.39. 610-617 (1998)

Kuroiwa S.等人：“视网膜缺血性损伤中垂死细胞中细胞周期相关基因的异常表达。”