权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Molecular Pathology of Rat Osteosarcoma and Malignant Fibrous Histiocytoma

大鼠骨肉瘤和恶性纤维组织细胞瘤的分子病理学

基本信息

批准号：
13671534
负责人：
MII Yoshio
金额：
$ 2.3万
依托单位：
Nara Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671534/
关键词：
Osteosarcoma Malignant Fibrous Histiocytoma Rat TGF-β Tyrosine kinase inhibitor p16 Methylation CDK inhibitor 悪性繊維性組織球腫 CDK cyclone D1 interleukins FHIT

项目摘要

1) We investigated TGF- β isoforms by Multi-probe RNA protection assay in COS1NR, COS2NR, COS4NR, MFH1NR and MFH2NR. The results showed TGF- β1to be strongly expressed and no TGF- β2 and 3 detected in MEHs, while TGF-β1 and 2 was found to be moderately and 3 weakly expressed in OS cell lines. No changes in TGF- βtype II receptor expression, and no mutations of TGF- β type II receptor, Smad2 and 4 genes were detected by RT-PCR and RT-PCR restricted SSCP analysis.2) The effect of STI571 was investigated on rat osteosarcoma and MFH cell lines. The cell growth of all cell lines was inhibited in a time- and dose-dependent manner. The inhibition rate were greater for MFH cell lines, about 40%, while about 20% for osteosarcoma cell lines. The difference of effectiveness was depend on PDGFR α expression.3) We investigated the expression and methylation status of 16^<INK4a> gene in rat osteosarcoma and malignant fibrous histiocytoma as well as rat lung adenocarcinoma cell lines. The PCR-SSCP analysis showed no expression of p16 gene in lung adenocarcinoma, while similar expression in ostesarcomas and MFHs as normal fibroblasts. The region close to coding region was hypermethylated in osteosarcoma, in contrast, the region nearby TATA box was consistently methylated in lung adenocarcinoma, MFHs and fibroblasts were hypomethylated in both regions.4) The effect of HMR1275 was investigated on rat osteosarcoma, MFH cell lines and lung adenocarcinoma cell lines. The cell growth of all cell lines was inhibited in a time- and dose-dependent manner. The inhibition rate were the greatest for lung adenocarcinoma cell lines, about 80%, while about 60% for osteosarcoma and MFH cell lines. The induction of p16 gene by the treatment of 5-aza 2'-deoxycytidine enhances the effects of HMR1275.

1)采用多探针β保护分析技术，研究了四种天然橡胶中的转化生长因子-H1NR亚型。结果显示，转化生长因子-β1在MEHS中强表达，未检测到转化生长因子-β2和3，而转化生长因子-β1和2在OS细胞中低表达，3在OS细胞中弱表达。逆转录-聚合酶链式反应和RT-β限制性单链构象多态性分析未检测到转化生长因子-βII型受体表达的变化，也未检测到转化生长因子-Smad2和Smad4基因的突变。所有细胞系的细胞生长均受到抑制，呈时间和剂量依赖性。MFH细胞株的抑制率较高，约为40%，骨肉瘤细胞株的抑制率约为20%。3)研究了大鼠骨肉瘤、恶性纤维组织细胞瘤和大鼠肺腺癌细胞系中16^-lt；INK4a和GT基因的表达和甲基化状态。聚合酶链式反应-单链构象多态性分析显示p16基因在肺腺癌中无表达，而在骨肉瘤和MFH中的表达与正常成纤维细胞相似。HMR1275对大鼠骨肉瘤、MFH细胞株和肺腺癌细胞株的作用进行了研究。所有细胞系的细胞生长均受到抑制，呈时间和剂量依赖性。对肺腺癌细胞的抑制率最大，约为80%，对骨肉瘤和MFH细胞的抑制率约为60%。5-氮-2‘-脱氧胞苷对p16基因的诱导增强了HMR1275的作用。