A study on ETS-1 as a terget molecle for antiangigenic therapy against cancer

ETS-1作为抗癌血管生成靶分子的研究

• 批准号: 10671231
• 负责人: OGATA Yutaka
• 金额: $ 2.11万
• 依托单位: Kurume University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671231/
• 关键词: ETS-1; Angiogenesis; differential display; bFGF; VEGF; HOMEC; u-PA; MMPs; Angic genesis; Colorectal cancer; vaccular endothelial growth factor (VEGF); Angiogenesis; 大腸癌; 微小血管密度; 血管内皮細胞; differential display method; vascular endothelialgrow

Immunohistochemical studies using surgically resected specimens from colorectal cancer patients and esophageal cancer patients indicated that the VEGF expression by the tumor cells and its receptor KDR expression by the endothelial cells correlated with the microvessel density (MVD), and that the VEGF expression or its combined expression with KDR might be an independent prognostic factor. We also found a correlation between the ETS- 1 expression by the endothelial cells, and the VEGF and pyrirnidine nucleotide (PyNPase) expression in colorectal cancer. Moreover, the ETS- 1 expression was found to be an independent prognostic factor in colorectal cancer.The expression of transcription factor ETS-1 was induced in endothelial cells (HOMEC) by bFGF. Differential display and western blot analysis showed that ETS-1 induced u-PA and MMP-l that related with angiogenesis. ETS-1 was found to induce gp96 mRNA in HOMEC.These results suggested that ETS-l might be candidate as a target molecule for anti-angiogenic therapy. We have to evaluate a significance of heat shock protein gp96 in relation to angiogenesis.

应用手术切除的结直肠癌和食道癌标本进行免疫组织化学研究表明，肿瘤细胞的血管内皮生长因子及其受体KDR的表达与微血管密度(MVD)相关，VEGF的表达及其与KDR的联合表达可能是一个独立的预后因素。结直肠癌组织中内皮细胞Ets-1的表达与血管内皮生长因子和吡啶核苷酸(PyNPase)的表达之间也存在相关性。此外，Ets-1的表达被发现是结直肠癌的独立预后因素。转录因子Ets-1的表达是由碱性成纤维细胞生长因子诱导内皮细胞(HOMEC)表达的。差异显示和免疫印迹分析表明，Ets-1诱导了与血管生成相关的u-PA和MMP一-L。Ets-1可诱导HOME细胞中gp96mRNA的表达，提示Ets-L可能成为抗血管生成治疗的靶分子。我们必须评估热休克蛋白gp96在血管生成中的意义。

项目成果

緒方 裕: "大腸癌の臨床特性と血管新生因子"G.I.Research. 6・5. 367-373 (1998)

Yutaka Ogata：“结直肠癌的临床特征和血管生成因素”G.I.Research 6・5（1998）。

Yoshikazu Harada: "Expression of vascular endothelial growth factor and its receptor KDR (kinase domain-containing receptor/Flk-1 liver kinase-1) as prognostic factors in human colorectal cancer"Int.J.Clin.Oncol.. 6・5. 221-228 (2001)

Yoshikazu Harada：“血管内皮生长因子及其受体 KDR（含有激酶结构域的受体/Flk-1 肝激酶-1）作为人类结直肠癌预后因素的表达”Int.J.Clin.Oncol.. 6・5。 221-228 (2001)