Analysis of Gene Expression Encoding Bone Matrix Proteins in Bone-Related Tumors

骨相关肿瘤中编码骨基质蛋白的基因表达分析

• 批准号: 11138232
• 负责人: NOMURA Shintaro
• 金额: $ 3.2万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas (A)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 无数据
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11138232/
• 关键词: Osteosarcoma; Metastasis; Osteopontin; Bone matrix protein; Transgenic Mice; In situ hybridization; Transcription factor; PEBP2α

Histological features of osteogenic tumor are affected of gene expression encoding bone matrix proteins. Therefore, pathological determination of osteogenic tumors, paticularly atipysm, may results of the abnormal gene expression of bone matrix proteins. We examined gene expression patterns encoding bone matrix proteins with surgically-obtained samples and analyzed by northern hybridization and in situ hybridization. Among samples examined, we observed abnormal expression of osteopontin mRNA in the highly metastatic osteosarcoma. These osteosarcomas had different gene expression pattern with normal cells. To investigate the mechanism of upregulated expression of osteopontin gene, the expression of major transcription factors such as PEBP2 alpfa-A and Ets-1 has examined. We detected mRNAs encoding these transcription factors with higher levels in compared to non-metastatic osteosarcoma. In addition, we generated transgenic mice carrying promoter region of osteopontin gene jointed with reoprter gene. some of these trasgenic line showed expression of reporter gene with the manner similar to the normal expression pattern of endogenous osteopontin gene.

骨基质蛋白基因表达影响成骨肿瘤的组织学特征。因此，骨源性肿瘤，特别是骨肉瘤的病理决定可能是骨基质蛋白基因表达异常的结果。我们研究了编码骨基质蛋白的基因表达模式，并通过北方杂交和原位杂交进行分析。在检测的标本中，我们观察到骨桥蛋白mRNA在高转移性骨肉瘤中的异常表达。这些骨肉瘤具有与正常细胞不同的基因表达模式。为了研究骨桥蛋白基因表达上调的机制，检测了主要转录因子如PEBP 2 α-A和Ets-1的表达。与非转移性骨肉瘤相比，我们检测到编码这些转录因子的mRNA水平更高。此外，我们还制备了骨桥蛋白基因启动子区与reopter基因连接的转基因小鼠。其中一些转基因株显示报告基因的表达，其方式与内源性骨桥蛋白基因的正常表达模式相似。

项目成果

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