An analysis of gene expression profile of osteosarcoma cells in the bone and peripheral blood with DNA microarray. -Identification of marker genes for osteosarcoma using hierarchical clustering algorithm. -

利用 DNA 微阵列分析骨和外周血中骨肉瘤细胞的基因表达谱。

• 批准号: 14370456
• 负责人: HOTTA Tetsuo
• 金额: $ 3.71万
• 依托单位: NIIGATA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 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-14370456/
• 关键词: osteosarcoma; DNA microarray; u-PA; SOD; DDR1; p53; cdk4; mdm2; DDRI; DNAマイクロアレイ; 遺伝子発現; エストロゲン; プラスミノーゲン; オキシジェンフリーラジカル; ptk-3; 末梢血

DNA microarray-based analysis of mRNA expression of 5147 genes in bone tissue was performed. Differentially expressed genes were identified by hierarchical clustering and scatter plot analyses. Differential mRNA expression of four genes [collagen type 2 (COL2), extracellular superoxide dismutase (SOD), plasminogen activator (u-PA) and DDR1] were confirmed by reverse transcription polymerase chain reaction. Further, immunohistologically, u-PA was positive for chondrocytes and chondroclasts in the junction between cartilage and bone, implying its importance in resorption and remodeling of cartilaginous cartilage. DDR1 is upregulated by irradiation in osteosarcoma cells and is regulated by p53, which is one of most important tumor suppressor genes. Known function strongly suggest important roles for DDR1 genes in the tumorigenesis of osteosarcoma. We also identified cdk4 and mdm2 genes, which are cell cycle related genes and are regulated by p53 gene, are overexpressed in well-differentiated liposarcoma. These genes are potential marker for distinguish lipoma and well-differentiated liposarcoma.

对骨组织中5147个基因的mRNA表达进行了基于DNA微阵列的分析。通过系统聚类和散点图分析确定差异表达基因。逆转录聚合酶链反应证实了4个基因[胶原2型（COL 2），细胞外超氧化物歧化酶（SOD），纤溶酶原激活剂（u-PA）和DDR 1]的mRNA表达差异。此外，免疫组织学，u-PA是阳性的软骨细胞和软骨破细胞之间的连接软骨和骨，这意味着它的重要性，在吸收和重塑的软骨软骨。在骨肉瘤细胞中，辐射可上调DDR 1的表达，并受最重要的抑癌基因之一p53的调节。已知的功能强有力地表明DDR 1基因在骨肉瘤的肿瘤发生中的重要作用。我们还发现，cdk 4和mdm 2基因，这是细胞周期相关基因，并受p53基因的调控，在高分化脂肪肉瘤中过表达。这些基因是鉴别脂肪瘤和高分化脂肪肉瘤的潜在标志物。

项目成果

Hatano H, Ogose A, Hotta T, et al.: "Treatment of myxoid liposarcoma by marginal or intralesional resection combined with radiotherapy."Anticancer Research. 23. 3045-3049 (2003)

Hatano H、Ogose A、Hotta T 等人：“通过边缘或病灶内切除结合放射治疗治疗粘液样脂肪肉瘤。”抗癌研究。

Hatano H, Sarkar G, Siegel HJ, et al.: "Identification of estrogen-regulated genes during fracture healing using DNA microarray"Jornal of Bone and Mineral Metabolism. In press. (2004)

Hatano H、Sarkar G、Siegel HJ 等人：“使用 DNA 微阵列识别骨折愈合过程中的雌激素调节基因”《骨与矿物质代谢杂志》。

Ogose A, Yazawa Y, Ueda T, Hotta T, et al.: "Alveolar soft part sarcoma in Japan : multi-institutional study of 57 patients from the Japanese Musculoskeletal Oncology Group."Oncology. 65. 7-13 (2003)

Ogose A、Yazawa Y、Ueda T、Hotta T 等人：“日本腺泡软组织肉瘤：对来自日本肌肉骨骼肿瘤学组的 57 名患者进行的多机构研究。”肿瘤学。

堀田哲夫他: "仙骨脊索腫の治療成績"整形外科. 53. 1125-1131 (2002)

Tetsuo Hotta 等：“骶骨脊索瘤的治疗结果”骨科 53. 1125-1131 (2002)

Hatano H, Sarkar G, Siegel HJ, et al.: "Identification of estrogen-regulated genes during fracture healing using DNA microarray."Journal of Bone and Mineral Metabolism. (in press). (2004)

Hatano H、Sarkar G、Siegel HJ 等人：“使用 DNA 微阵列识别骨折愈合过程中的雌激素调节基因。”骨与矿物质代谢杂志。