Identification of new therapeutic target molecules for renal cell carcinoma

• Project/Area Number: 24659712
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Urology
• Research Institution: Kyoto University
• Principal Investigator: NAKAMURA Eijiro 京都大学, 医学(系)研究科(研究院), 准教授 (90293878)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 腎細胞癌 / VHL / Renal Cell Carcinoma

Research Abstract

Recently, the number of RCC patients is increasing. Although, anti-VEGF therapies improve the prognosis of those patients, most of tumors acquire resistance and finally progress. It has been reported that VHL gene is mutated in 70% of RCC and we showed that clusterin was regulated by pVHL. It was suggested clusterin had a tumor suppressor function since this molecule is down regulated by pVHL. Based on these, we have cloned the promoter region of clusterin to examine the regulation mechanisms of the protein as well as the identification of new therapeutic target for RCC. As a result of this, MAP2K1 was identified as new molecular therapeutic target for RCC.

Research Products

• [Journal Article] SQSTM1 Is a Pathogenic Target of 5q Copy Number Gains in Kidney Cancer (2013)
  • Author(s): Li L, Shen C, E Nakamura, Ando K, Signoretti S, Beroukhim R, Cowley GS, Lizotte P, Liberzon E, Bair S, Root DE, Tamayo P, Tsherniak A, Cheng SC, Tabak B, Jacobsen A, Hakimi AA, Schultz N, Ciriello G, Sander C, Hsieh JJ, Kaelin WG Jr
  • Journal Title: Cancer Cell Volume: 24(6) Pages: 738-50
• [Journal Article] The transcription factor Sp3 regulates the expression of a metastasis-related marker of sarcoma, actin filament-associated protein 1-like 1 (AFAP1L1) (2013)
  • Author(s): Kajita Y, Kato T Jr, Tamaki S, Furu M, Takahashi R, Nagayama S, Aoyama T, Nishiyama H, E Nakamura, Katagiri T, Nakamura Y, Ogawa O and Toguchida J
  • Journal Title: PLoS One Volume: 8(1) Pages: 49709-49709
• [Journal Article] Downregulation of Ral GTPase activating protein promotes tumor invasion and metastasis of bladder cancer (2013)
  • Author(s): Saito R, Shirakawa R, Nishiyama H, Kobayashi T, Kawato M, Kanno T, Nishizawa K, Matsui Y, Ohbayashi T, Horiguchi M, Nakamura T, Ikeda T, Yamane K, Nakayama E, E Nakamura, Toda Y, Kimura T, Kita T, Ogawa O and Horiuchi H
  • Journal Title: Oncogene Volume: 32(7) Pages: 894-902
• [Journal Article] SQSTM1 is a pathogenic target of 5q copy number gains in kidney cancer. (2013)
  • Author(s): Li L, Shen C, Nakamura E, Ando K, Signoretti S, Beroukhim R, Cowley GS, Lizotte P, Liberzon E, Bair S, Root DE, Tamayo P, Tsherniak A, Cheng SC, Tabak B, Jacobsen A, Hakimi AA, Schultz N, Ciriello G, Sander C, Hsieh JJ, Kaelin WG Jr
  • Journal Title: Cancer Cell Volume: 24 Issue: 6 Pages: 738-750
  • DOI: 10.1016/j.ccr.2013.10.025
  • Peer Reviewed
• [Journal Article] The Transcription Factor Sp3 Regulates the Expression of a Metastasis-Related Marker of Sarcoma, Actin Filament-Associated Protein 1-Like 1 (AFAP1L1). (2013)
  • Author(s): Kajita Y, Kato T Jr, Tamaki S, Furu M, Takahashi R, Nagayama S, Aoyama T, Nishiyama H, Nakamura E, Katagiri T, Nakamura Y, Ogawa O, Toguchida J.
  • Journal Title: PLoS One Volume: 8 Issue: 1 Pages: e49709-e49709
  • DOI: 10.1371/journal.pone.0049709
  • Peer Reviewed
• [Journal Article] Tumor microvasculature with endothelial fenestrations in VHL null clear cell renal cell carcinomas as a potent target of anti-angiogenic therapy (2012)
  • Author(s): Yamasaki T, Kamba T, Kanno T, Inoue T, Shibasaki N, Arakaki R, Yamada T, Kondo K, Kamoto T, Nishiyama H, Ogawa O and E Nakamura
  • Journal Title: Cancer Sci Volume: 103(11) Pages: 2027-37
• [Journal Article] Downregulation of Ral GTPase-activating-protein causes tumor invasion and metastasis of bladder cancer (2012)
  • Author(s): R.Saito
  • Journal Title: Oncogene Volume: (未定)(In press) Issue: 7 Pages: 894-902
  • DOI: 10.1038/onc.2012.101
  • Peer Reviewed
• [Journal Article] Tumor microvasculature with endothelial fenestrations in VHL null clear cell renal cell carcinomas as a potent target of anti-angiogenic therapy. (2012)
  • Author(s): Yamasaki T, Kamba T, Kanno T, Inoue T, Shibasaki N, Arakaki R, Yamada T, Kondo K, Kamoto T, Nishiyama H, Ogawa O, Nakamura E.
  • Journal Title: Oncogene Volume: 103 Pages: 2027-2037
  • Peer Reviewed
• [Journal Article] JunB promotes cell invasion and angiogenesis in VHL-defective renal cell carcinoma. (2012)
  • Author(s): Kanno T, Kamba T, Yamasaki T, Shibasaki N, Saito R, Terada N, Toda Y, Mikami Y, Inoue T, Kanematsu A, Nishiyama H, Ogawa O, Nakamura E.
  • Journal Title: Oncogene Volume: 31 Pages: 3098-110
  • Peer Reviewed
• [Remarks]
  • URL: http://www.dsk.med.kyoto-u.ac.jp/