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

点击翻译按钮获取中文摘要

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).