Development of novel therapy

• Project/Area Number: 15591701
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Urology
• Research Institution: Yokohama City University
• Principal Investigator: NAKAIGAWA Noboru Yokohama City University, Hospital, associate professor, 医学部附属病院, 講師 (00237207)
• Co-Investigator(Kenkyū-buntansha): YAO Masahiro Yokohama City University, School of Medicine, associate professor, 医学系研究院, 助教授 (00260787) ; KISHIDA Takeshi Yokohama City University, Hospital, associate professor, 医学部附属病院, 講師 (60254166)
• Project Period (FY): 2003 – 2004
• Project Status: Completed (Fiscal Year 2004)
• Budget Amount: ¥3,500,000 (Direct Cost: ¥3,500,000); Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000); Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
• Keywords: renal cell carcinoma / MET protein / VHL gene / ヒト腎癌細胞 / 腫瘍マーカー / 治療ターゲット / 2次元泳動

Research Abstract

We screened the expression levels and activation levels of intrace Ilular protein in human renal cell carcinoma cells and found that the activation of some protein associated intracellulax signal transduction pathways were accelerated in cancer cells. MET protein, the tyrosine kinase receptor for hepatocyte growth factor/scattering factor was constitutive activated in human clear cell renal carcinoma, which occupied about 80% of human kidney cancer. The activation of MET protein was induced by the inactivation of VHL gene which predisposed human clear renal cell carcinoma, we found that MET protein in most of clear renal cell carcinoma tumor tissues gained from surgeries showed hyperphosphorylation compared with that in normal tissues. When activation of MET protein in CCRC cells was inhibited by the MET inhibitor K252a, the growth of CCRC cells in vitro and the tumorigenesis induced by CCRC cells in nude mice were suppressed. From these results, we concluded that MET protein played important roles in tumorigenesis of human kidney cancer. At the same time, the results suggested that MET protein has a potential as a molecular target for novel CCRC therapies.

Research Products

• [Journal Article] 淡明細胞型腎癌におけるMET蛋白の活性化についての検討 (2005)
  • Author(s): 中井川昇, 矢尾正祐, 加藤真吾, 岸田健, 長嶋洋治, 窪田吉信
  • Journal Title: 腎癌研究会会報 28 Pages: 15-16
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Gene expression analysis of renal carcinoma: adipose differentiation-related protein as a potential diagnostic and prognostic biomarker for clear-cell renal carcinoma (2005)
  • Author(s): Yao, M., Tabuchi, H., Nagashima, Y., Baba, M., Nakaigawa, N., Ishiguro, H., Hamada, K., Inayama, Y., Kishida, T., Hattori, K., Yamada-Okabe, H., Kubota
  • Journal Title: J Pathol. 205(3) Pages: 377-387
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Activation of MET protein in human clear cell renal carcinoma (2005)
  • Author(s): Nakaigawa, N., Yao, M., Kato, S., Kishida, T., Nagashima, Y., Kubota, Y.
  • Journal Title: Jingan Kennkyuukai Kaihou(Japanese) 28 Pages: 15-16
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Gene expression analysis of renal carcinoma : adipose differentiation-related protein as a potential diagnostic and prognostic biomarker for clear-cell renal carcinoma. (2004)
  • Author(s): Yao M, Tabuchi H, Nagashima Y, Baba M, Nakaigawa N, Ishiguro H, Hamada K, Inayama Y, Kishida T, Hattori K, Yamada-Okabe H, Kubota
  • Journal Title: J Pathol. 205(3) Pages: 377-387
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Loss of von Hippel-Lindau protein causes cell density dependent deregulation of cyclinD1 expression through hypoxia-inducible factor. (2003)
  • Author(s): Baba M, Hirai S, Yamada-Okabe H, Hamada K, Tabuchi H, Kobayashi K, Kondo K, Yoshida M, Yamashita A, Kishida T, Nakaigawa N, Nagashima Y, Kubota Y, Yao M, Ohno S
  • Journal Title: Oncogene 22(18) Pages: 2728-2738
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Loss of von Hippel-Lindau protein causes cell density dependent deregulation of CyclinD1 expression through hypoxia-inducible factor (2003)
  • Author(s): Baba, M., Hirai, S., Yamada-Okabe, H., Hamada, K., Tabuchi, H., Kobayashi, K., Kondo, K., Yoshida, M., Yamashita, A., Kishida, T., Nakaigawa, N., Nagashima, Y., Kubota, Y., Yao, M., Ohno, S.
  • Journal Title: Oncogene. 22(18) Pages: 2728-2738
  • Description: 「研究成果報告書概要(欧文)」より