in vitro manipulation of genes relevant to oncogenesis

体外操作与肿瘤发生相关的基因

• 批准号: 06454608
• 负责人: SASAZUKI Takehiko
• 金额: $ 4.48万
• 依托单位: Medical Institute of Bioregulation, Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06454608/
• 关键词: Colon cancer cell lines; homologous recombination; K-ras gene; 大腸癌細胞株; 血管内皮増殖因子; K-ras; P53; 相同組み換え

We have established the colon cancer cell lines in which the mutated K-ras gene was replaced by the normal K-ras gene, using homologous recombination. The comparative analyzes between these cell lines and the parental cell lines made it feasible to directly assess the role of the mutated K-ras gene in oncogenesis. As compared with the parental cell lines, the cell lines which lack the expression of the mutated K-ras gene showed the remarkable induction of C-fos and C-jun expression by the serum stimulation and the suppression of vascular endothelial growth factor (VEGF) production. These observations indicate that the mutated K-ras gene is involved in the suppression of the immediate early genes expression and the production of VEGF.Our strategy could be applied to clarify the role of the mutation in other oncogenes and tumor suppressor genes in oncogenesis.

我们利用同源重组技术，建立了突变K-ras基因被正常K-ras基因取代的结肠癌细胞系。这些细胞系与亲本细胞系的比较分析使得直接评估突变的K-ras基因在肿瘤发生中的作用是可行的。与亲本细胞株相比，突变K-ras基因表达缺失的细胞株在血清刺激下表现出明显的C-fos和C-jun表达，并抑制了血管内皮生长因子(VEGF)的产生。这些观察结果表明，突变的K-ras基因参与了抑制即刻早期基因的表达和VEGFF的产生，我们的策略可以用于阐明其他癌基因和抑癌基因的突变在肿瘤发生中的作用。

项目成果

J.Rak, Y.Mitsuhashi, L.Bayko, J.Filmus, S.Shirasawa, T.Sasazuki, and R.S.Curbel: "Mutant ras oncogenes upregulate VEGF/VPF expression : Implications for induction and inhibition of tumor angiogenesis" Cancer Research. vol.55. 4575-4580 (1995)

J.Rak、Y.Mitsuhashi、L.Bayko、J.Filmus、S.Shirasawa、T.Sasazuki 和 R.S.Curbel：“突变 ras 癌基因上调 VEGF/VPF 表达：对诱导和抑制肿瘤血管生成的影响”癌症研究。

Rae SM.Yeung: "Human CD4-major histocompatibility complex class II(DQW6) transgenic mice in an endogenous CD4/CD8-deficient background:Reconstitution of phenotype and human restrieted function." J.Exp.Med.180. 1911-1920 (1994)

Rae SM.Yeung：“在内源性 CD4/CD8 缺陷背景下的人类 CD4 主要组织相容性复合物 II 类 (DQW6) 转基因小鼠：表型和人类重新调整功能的重建。”

Yamamoto K.: "Functional interaction between human histocompatibility leukocyte antigen (HLA)class II and mouse CD4 molecule in antigen tecognition by T cells in HLA-DR and DQ transgenic mice." J.Exp.Med.180. 165-171 (1994)

Yamamoto K.：“人类组织相容性白细胞抗原 (HLA) II 类和小鼠 CD4 分子在 HLA-DR 和 DQ 转基因小鼠 T 细胞抗原识别中的功能相互作用。”

J. Rak et al.: "Mutant ras oncogenes upregulate VEGF/VPF expression: Implications for induction and inhibition of tumor angiogenesis" Cancer Research. 55. 4575-4580 (1995)

J. Rak 等人：“突变 ras 癌基因上调 VEGF/VPF 表达：对诱导和抑制肿瘤血管生成的影响”癌症研究。

J. Rak: "Mutant ras oncogenes upregulate VEGF/VPF expression: Implications for induction and inhibition of tumor angiogenesis" Cancer Research. 55. 4575-4580 (1995)

J. Rak：“突变 ras 癌基因上调 VEGF/VPF 表达：对诱导和抑制肿瘤血管生成的影响”癌症研究。