Discovery of targets for treatment with renal cell carcinoma by gene and protein expression profile analysis

通过基因和蛋白质表达谱分析发现肾细胞癌治疗靶点

• 批准号: 16390040
• 负责人: OKUMURA Katsuhiko
• 金额: $ 8.38万
• 依托单位: Kobe University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390040/
• 关键词: Proteome analysis; Transcriptome analysis; Renal cell carcinoma; Sorcin; VEGF; MALDI-TOF; Ms; MDR1; sorcin; EGFR; 遺伝子型

Renal cell carcinoma (RCC) is one of the most chemotherapy or radiotherapy-resistant malignant tumors, and therefore, the standard therapy is surgical treatment. Also, there is no efficient biomarker for diagnosis. To elucidate resistant mechanisms and discovery novel targets for treatment and biomarker for diagnosis, transcriptome and proteome analysis were carried out using RCC and adjacent normal tissues.Since lower expression of sorcin in RCC was found, we investigated its role in cancer proliferation by RNA interference. Up-regulation of vascular endothelial growth factor (VEGF), a potent angiogenesis factor contributing to cancer proliferation, was found by knock-down of sorcin using siRNA in renal cell carcinoma cells, Caki-1. This suggested that lower expression of sorcin caused up-regulation of VEGF, thereby lead cancer proliferation.To comprehensive analysis of protein expressions in RCC and adjacent normal tissues, samples were labeled with 2-nitrobeazenesulfonyl chloride with six ^<12>C or ^<13>C atoms. Then, they were applied MALDI-TOF/Ms and pair peak of 6 Da difference were analyzed and identified. Unknown proteins were identified in addition to known proteins, which have been reported to be up-regulated in RCC.

肾细胞癌（RCC）是对化疗或放疗最耐药的恶性肿瘤之一，因此标准治疗是手术治疗。此外，还没有有效的生物标志物用于诊断。为了阐明耐药机制并发现新的治疗靶点和诊断生物标志物，使用 RCC 和邻近正常组织进行了转录组和蛋白质组分析。由于发现 RCC 中 sorcin 表达较低，我们通过 RNA 干扰研究了其在癌症增殖中的作用。通过在肾细胞癌细胞 Caki-1 中使用 siRNA 敲除 sorcin，发现血管内皮生长因子 (VEGF) 上调，VEGF 是一种有助于癌症增殖的有效血管生成因子。这表明sorcin的低表达引起VEGF的上调，从而导致癌症增殖。为了综合分析RCC和癌旁正常组织中的蛋白表达，样品用6^<12>C或^<的2-硝基苯磺酰氯标记。 13>C原子。然后，应用MALDI-TOF/Ms对6Da差异的峰进行分析和鉴定。除了已知蛋白质外，还鉴定出未知蛋白质，据报道这些蛋白质在肾细胞癌中表达上调。

项目成果

MDR1 C3435T Polymorphism is predictive of later onset of ulcerative colitis in Japanese

MDR1 C3435T 多态性可预测日本人溃疡性结肠炎的晚期发作

• 发表时间: 2006
• 作者: Osuga T

Antiproliferative activity of Rhinacanthus nasutus (L.) Kurz extracts and the active moiety, Rhinacanthin C.

Rhinacanthus nasutus (L.) Kurz 提取物及其活性部分 Rhinacanthin C 的抗增殖活性。

• 发表时间: 2004
• 作者: Gotoh A

EGFR mRNA is upregulated, but somatic mutaions of the gene are hardly found in renal cell carcinoma in Japanese patients

日本肾细胞癌患者EGFR mRNA上调，但几乎未发现该基因的体细胞突变

• 发表时间: 2005
• 作者: Sakaeda T

Association of VEGF genotype with mRNA level in colorectal adenocarcinomas.

结直肠腺癌中 VEGF 基因型与 mRNA 水平的关联。

• DOI: 10.1016/j.bbrc.2004.10.005
• 发表时间: 2004-12-03
• 期刊: Biochemical and biophysical research communications
• 影响因子: 3.1
• 作者: M. Yamamori;T. Sakaeda;Tsutomu Nakamura;N. Okamura;T. Tamura;N. Aoyama;T. Kamigaki;M. Ohno;T. Shirakawa;A. Gotoh;Y. Kuroda;M. Matsuo;M. Kasuga;K. Okumura
• 通讯作者: K. Okumura

Effect of micafungin on cytochrome P450 3A4 and multidrug resistance protein 1 activities, and its comparison with azole antifungal drugs

米卡芬净对细胞色素P450 3A4和多药耐药蛋白1活性的影响及其与唑类抗真菌药物的比较

• DOI: 10.1211/0022357056118
• 发表时间: 2005-06-01
• 期刊: Journal of Pharmacy and Pharmacology
• 影响因子: 3.3
• 作者: T. Sakaeda;K. Iwaki;M. Kakumoto;Mika Nishikawa;T. Niwa;Jiang;Tsutomu Nakamura;K. Nishiguchi;N. Okamura;K. Okumura
• 通讯作者: K. Okumura