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).

我们以前已经报道了细胞周期调节剂分子的几种不同功能。在该研究项目中，与肺癌相比，使用培养细胞以及骨肉瘤的人类手术材料进行了更详细的分析。并且，我们阐明了以下内容。作为肺癌（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，而且由降解系统受到多种调节，具体取决于组织学类型。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，积累为激酶无活性形式而没有蛋白酶体系统中没有降解（J.Pathol。2003）.IV）表皮生长因子受体（EGFR）在7至15％的病例中过表达了胃肠道的癌症中的7至15％的胃肠道（模型），并且是由基因表达的。 2004）.v）在2％的骨骼和软组织肉瘤中观察到EGFR的过表达，这些病例仅与基因异常有关，即放大和多症（手稿）。