Functional analysis and clinical application of PHD3 in renal cell carcinoma
| Project/Area Number |
22791477
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Urology
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
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| Project Period (FY) |
2010 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| 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)
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| 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 |
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| 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.
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Report
(3 results)
Research Products
(12 results)
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[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.
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Journal Title
J. Cancer Res. Clin. Oncol
Volume: 137
Issue: 5
Pages: 789-794
DOI
Related Report
Peer Reviewed
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