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Analyses for abnormality of cell cycle regulator molecules and their application to diagnosis and therapy in bone and soft tissue tumors

细胞周期调节分子异常分析及其在骨和软组织肿瘤诊断和治疗中的应用

基本信息

批准号：
14570161
负责人：
DOBASHI Yoh
金额：
$ 2.24万
依托单位：
University of Yamanashi (2003)山梨医科大学 (2002)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570161/
关键词：
Soft tissue tumors Cell cycle Apoptosis Lung carcinoma EGFR Cyclin Cdk AMF

项目摘要

We have previously reported several diverse functions of cell cycle regulator molecules. In this research project, more detailed analysis was performed using cultured cells as well as human surgical materials of osteosarcoma in comparison to those of lung carcinomas. And, we clarified the followings.i) Overexpression of cyclin D1 or ccdk4, which cause apoptosis in neuronal cultured cells, also caused apoptosis in osteosarcoma and in other cultured cells (Anticancer Res. 2003, Curr. Medic. Chem. 2003).ii) Furthermore, apoptosis induced by overexpression of cyclin D1/cdk4 was observed in human tumors, such as lung carcinomas (Int. J. Cancer 2004).iii) The protein levels of cyclins/cdks were diversely regulated not only by their expression, but also by degradation system, depending on the histological types. In lung carcinoma, cyclin A is highly expressed in proliferating cells and rapidly degraded. However, cyclin E, specifically in squamous cell carcinoma, is accumulated as kinase-inactive-form without degradation in proteasome system (J. Pathol. 2003).iv) Epidermal growth factor receptor (EGFR) is overexpressed in 7 to 15% of the cases in carcinomas of gastrointestinal tract, and overexpression is predominantly caused by gene amplification (Mod. Pathol. 2004).v) Overexpression of EGFR was observed in 2% of bone and soft tissue sarcomas, and those cases were exclusively associated with gene abnormality, i.e., amplification and polysomy (manuscript submitted).

我们以前曾报道过几种不同的细胞周期调节分子的功能。在本研究项目中，使用培养的细胞以及骨肉瘤的人类手术材料进行了更详细的分析，并与肺癌进行了比较。i）引起神经元培养细胞凋亡的细胞周期蛋白D1或ccdk 4的过表达也引起骨肉瘤和其它培养细胞的凋亡（Anticancer Res.2003，Curr.医生ii）此外，在人肿瘤如肺癌中观察到由细胞周期蛋白D1/cdk 4的过表达诱导的细胞凋亡（Int. J. Cancer 2004）。iii）细胞周期蛋白/cdk的蛋白质水平不仅通过其表达，而且通过降解系统，取决于组织学类型，受到不同程度的调节。在肺癌中，细胞周期蛋白A在增殖细胞中高度表达并迅速降解。然而，细胞周期蛋白E，特别是在鳞状细胞癌中，在蛋白酶体系统中以激酶失活形式积累而不降解（J. Pathol. iv）表皮生长因子受体（EGFR）在7 - 15%的胃肠道癌病例中过表达，并且过表达主要由基因扩增引起（Mod.Pathol.2003）。v）在2%的骨和软组织肉瘤中观察到EGFR的过表达，并且这些病例仅与基因异常相关，即，扩增和多体性（手稿提交）。