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）是最耐化疗或放疗的恶性肿瘤之一，因此，手术治疗是标准的治疗方法。此外，没有有效的生物标志物进行诊断。为了阐明耐药机制，发现新的治疗靶点和诊断生物标志物，研究人员对RCC和邻近正常组织进行了转录组和蛋白质组分析。由于sorcin在RCC中表达较低，我们通过RNA干扰研究了sorcin在肿瘤增殖中的作用。血管内皮生长因子（VEGF）是一种促进癌症增殖的有效血管生成因子，通过在肾癌细胞Caki-1中使用siRNA敲除sorcin发现其上调。这表明sorcin的低表达引起VEGF的上调，从而导致肿瘤的增殖。为了全面分析RCC和邻近正常组织中的蛋白表达，样品被标记为含有6个^<12>C或^<13>C原子的2-硝基苯磺酰氯。然后应用MALDI-TOF/Ms，对6 Da差异的对峰进行分析鉴定。除了已知蛋白外，还鉴定出未知蛋白，据报道，这些蛋白在RCC中上调。

项目成果

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

• DOI: 10.1007/s11095-005-7094-2
• 发表时间: 2005-10-01
• 期刊: PHARMACEUTICAL RESEARCH
• 影响因子: 3.7
• 作者: Sakaeda, T;Okamura, N;Okumura, K
• 通讯作者: Okumura, K

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

• DOI: 10.1248/bpb.27.1070
• 发表时间: 2004-07-01
• 期刊: BIOLOGICAL & PHARMACEUTICAL BULLETIN
• 影响因子: 2
• 作者: Gotoh, A;Sakaeda, T;Okumura, K
• 通讯作者: Okumura, K

Carvedilol: a new candidate for reversal of MDR1/P-glycoprotein-mediated multidrug resistance

• DOI: 10.1097/00001813-200404000-00001
• 发表时间: 2004-04
• 期刊: Anti-Cancer Drugs
• 影响因子: 2.3
• 作者: K. Takara;T. Sakaeda;K. Okumura

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
• 期刊: Biological and Pharmaceutical Bulletin 第29巻・第2号
• 作者: Nishimura T;Ogihara T;Tsuji A;Akira Minami et al.;Atsushi Takeda et al.;Osuga T
• 通讯作者: Osuga T