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Functional analysis and clinical application of PHD3 in renal cell carcinoma

Research Project

Project/Area Number 22791477
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Urology
Research InstitutionSapporo Medical University

Principal Investigator

TANAKA Toshiaki  札幌医科大学, 医学部, 助教 (50398327)

Project Period (FY) 2010 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords腎細胞癌 / 腫瘍生物学 / 分子生物学 / 腫瘍免疫学 / シグナル伝達 / 腫瘍マーカー
Research Abstract

VHL gene-mutant cell lines of renal cell carcinoma(RCC), SMKT-R2 and SMKT-R3 had stable overexpression of PHD3. In Caki-1, a VHL-wild type RCC cell line, PHD3 expression was induced in the non-confluent state. In Caki-1, in the nonconfluent state, the PI3K/Akt/mTOR pathway was activated, and inhibition of the pathway with LY294002 reduced PHD3 expression. Even in HIF-la/2a double-knockdown Caki-1, activation of the PI3k/Akt/mTOR pathway induced overexpression of PHD3. In addition, PHD3 siRNA promoted cell proliferation compared with control siRNA in Caki-1 without induction of HIF protein expression. Even in VHL-mutant SMKT-R2 and SMKT-R3, PHD3 siRNA showed the same effect. On the other hand, PHD3-expressing plasmid transfection into ACHN, a RCC cell line with no expression of PHD3 under normoxia, reduced cell proliferation compared with empty vector transfection.
In 22 patients with RCC, preoperative serum anti-PHD3 Ab titers were significantly higher in RCC patients than in healthy volunteers. Both pre-and postoperative serum samples were obtained from 17 patients at least 1 month after tumor removal. In all 17 patients, titers of serum anti-PHD3 were decreased after the surgical resection compared with those before operation. The result suggests that the anti-PHD3 Ab may be a novel serological marker for RCC, and the titer may reflect the tumor burden in each individual.

Report

(3 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • Research Products

    (12 results)

All 2012 2011 2010

All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (10 results)

  • [Journal Article] Autoantibody against hypoxia-inducible factor prolyl hydroxylase-3 is a potential serological marker for renal cell carcinoma2011

    • Author(s)
      Tanaka, T., Kitamura, H., Torigoe, T., Hirohashi, Y., Masumori, N., Sato, N. and Tsukamoto, T.
    • Journal Title

      J. Cancer Res. Clin. Oncol

      Volume: 137 Issue: 5 Pages: 789-794

    • DOI

      10.1007/s00432-010-0940-6

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Autoantibody against hypoxia-inducible factor prolyl hydroxylase-3 is a potential serological marker for renal cell carcinoma2010

    • Author(s)
      Toshiaki Tanaka
    • Journal Title

      Journal of Cancer Research and Clinical Oncology

      Volume: (Published online)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] PHD3 expression is a predictor of progression-free survival in clear cell renal cell carcinoma2012

    • Author(s)
      Toshiaki Tanaka
    • Organizer
      第27回欧州泌尿器科学会総会
    • Place of Presentation
      フランス・パリ
    • Year and Date
      2012-02-25
    • Related Report
      2011 Annual Research Report
  • [Presentation] PHD3 expression is a predictor of progression-free survival in renal cell carcinoma2012

    • Author(s)
      Tanaka T, Kitamura H, Torigoe T, Hirohashi Y, Masumori N, Sato N, Tsukamoto T
    • Organizer
      27th European Association of Urology Congress
    • Place of Presentation
      Paris
    • Related Report
      2011 Final Research Report
  • [Presentation] PHD3 has a HIF-independent-antiproliferative function in renal cell carcinoma2010

    • Author(s)
      Tanaka T, Torigoe T, Hirohashi Y, Kitamura H, Masumori N, Tsukamoto T, Sato N
    • Organizer
      第69回日本癌学会総会
    • Place of Presentation
      大阪
    • Year and Date
      2010-09-22
    • Related Report
      2011 Final Research Report
  • [Presentation] HIF prolyl hydroxylase-3 has a HIF-independent-antiproliferative function in renal cell carcinoma2010

    • Author(s)
      田中俊明
    • Organizer
      第69回日本癌学会学術総会
    • Place of Presentation
      大阪
    • Year and Date
      2010-09-22
    • Related Report
      2011 Annual Research Report 2010 Annual Research Report
  • [Presentation] PHD3 is expressed independently of HIFprotein and has a HIF-independent anti-proliferative function in renal cell carcinoma : the novel expression mechanism and function2010

    • Author(s)
      Tanaka T, Torigoe T, Hirohashi Y, Kitamura H, Masumori N, Tsukamoto T, Sato N
    • Organizer
      21st European Association for Cancer Research
    • Place of Presentation
      Oslo
    • Year and Date
      2010-06-29
    • Related Report
      2011 Final Research Report
  • [Presentation] PHD3 is expressed independently of HIF protein and has a HIF-independent anti-proliferative function in renal cell carcinoma : the novel expression mechanism and function2010

    • Author(s)
      Toshiaki Tanaka
    • Organizer
      第21回欧州癌研究学会総会
    • Place of Presentation
      ノルウェー・オスロ
    • Year and Date
      2010-06-29
    • Related Report
      2011 Annual Research Report 2010 Annual Research Report
  • [Presentation] American Urology Association 2010. PHD3 has a HIF-independent-antiproliferative function in renal cell carcinoma2010

    • Author(s)
      Tanaka T, TorigoeT, Hirohashi Y, Sato E, Honma I, Kitamura H, Masumori N, Sato N, Tsukamoto T
    • Organizer
      American Urological Association Annual Meeting 2010
    • Place of Presentation
      San Francisco
    • Year and Date
      2010-05-30
    • Related Report
      2011 Final Research Report
  • [Presentation] PHD3 has a HIF-independent-antiproliferative function in renal cell carcinoma2010

    • Author(s)
      Toshiaki Tanaka
    • Organizer
      米国泌尿器科学会2010 Annual Meeting
    • Place of Presentation
      米国・サンフランシスコ
    • Year and Date
      2010-05-30
    • Related Report
      2011 Annual Research Report
  • [Presentation] PHD3 has a HIF-independent-antiproliferative function in renal cell carcinoma2010

    • Author(s)
      Toshiaki Tanaka
    • Organizer
      米国泌尿器科学会 2010 Annual Meeting
    • Place of Presentation
      米国・サンフランシスコ
    • Year and Date
      2010-05-30
    • Related Report
      2010 Annual Research Report
  • [Presentation] 腎細胞癌におけるPHD3の増殖抑制効果2010

    • Author(s)
      田中俊明
    • Organizer
      第98回日本泌尿器科学会学術総会
    • Place of Presentation
      盛岡
    • Year and Date
      2010-04-30
    • Related Report
      2011 Annual Research Report 2010 Annual Research Report

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Published: 2010-11-30   Modified: 2016-04-21  

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