Functional analysis and clinical application of PHD3 in renal cell carcinoma
PHD3在肾细胞癌中的功能分析及临床应用
基本信息
- 批准号:22791477
- 负责人:
- 金额:$ 2.16万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Young Scientists (B)
- 财政年份:2010
- 资助国家:日本
- 起止时间:2010 至 2011
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
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.
肾细胞癌(RCC)VHL基因突变细胞系SMKT-R2和SMKT-R3具有稳定的PHD 3过表达。在VHL-野生型RCC细胞系Caki-1中,在非融合状态下诱导PHD 3表达。在Caki-1中,在非融合状态下,PI 3 K/Akt/mTOR通路被激活,并且用LY 294002抑制该通路降低PHD 3表达。即使在HIF-1a/2a双敲低的Caki-1中,PI 3 k/Akt/mTOR通路的激活也诱导PHD 3的过表达。此外,与对照siRNA相比,PHD 3 siRNA在Caki-1中促进细胞增殖,而不诱导HIF蛋白表达。即使在VHL突变体SMKT-R2和SMKT-R3中,PHD 3 siRNA也显示出相同的效果。另一方面,将PHD 3表达质粒转染入ACHN(一种在常氧条件下不表达PHD 3的RCC细胞系)中,与空载体转染相比,细胞增殖减少。在22例RCC患者中,RCC患者术前血清抗PHD 3 Ab滴度显著高于健康志愿者。术前和术后的血清样本,从17例患者至少1个月后肿瘤切除。17例患者术后血清抗PHD 3抗体滴度均较术前下降。提示抗PHD 3抗体可作为肾细胞癌的血清学标志物,其滴度可反映个体的肿瘤负荷。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
腎細胞癌におけるPHD3の増殖抑制効果
PHD3对肾细胞癌的生长抑制作用
- DOI:
- 发表时间:2010
- 期刊:
- 影响因子:0
- 作者:Tanaka T;TorigoeT;Hirohashi Y;Sato E;Honma I;Kitamura H;Masumori N;Sato N;Tsukamoto T;Toshiaki Tanaka;Toshiaki Tanaka;田中俊明
- 通讯作者:田中俊明
American Urology Association 2010. PHD3 has a HIF-independent-antiproliferative function in renal cell carcinoma
美国泌尿外科协会 2010。PHD3 在肾细胞癌中具有不依赖 HIF 的抗增殖功能
- DOI:
- 发表时间:2010
- 期刊:
- 影响因子:0
- 作者:Tanaka T;TorigoeT;Hirohashi Y;Sato E;Honma I;Kitamura H;Masumori N;Sato N;Tsukamoto T
- 通讯作者:Tsukamoto T
Autoantibody against hypoxia-inducible factor prolyl hydroxylase-3 is a potential serological marker for renal cell carcinoma
抗缺氧诱导因子脯氨酰羟化酶 3 的自身抗体是肾细胞癌的潜在血清学标志物
- DOI:10.1007/s00432-010-0940-6
- 发表时间:2011
- 期刊:
- 影响因子:0
- 作者:Tanaka;T.;Kitamura;H.;Torigoe;T.;Hirohashi;Y.;Masumori;N.;Sato;N. and Tsukamoto;T.
- 通讯作者:T.
PHD3 expression is a predictor of progression-free survival in clear cell renal cell carcinoma
PHD3 表达是透明细胞肾细胞癌无进展生存的预测因子
- DOI:
- 发表时间:2012
- 期刊:
- 影响因子:0
- 作者:Tanaka;T.;Kitamura;H.;Torigoe;T.;Hirohashi;Y.;Masumori;N.;Sato;N. and Tsukamoto;T.;Toshiaki Tanaka;Toshiaki Tanaka
- 通讯作者:Toshiaki Tanaka
HIF prolyl hydroxylase-3 has a HIF-independent-antiproliferative function in renal cell carcinoma
HIF 脯氨酰羟化酶 3 在肾细胞癌中具有不依赖 HIF 的抗增殖功能
- DOI:
- 发表时间:2010
- 期刊:
- 影响因子:0
- 作者:Tanaka T;Torigoe T;Hirohashi Y;Kitamura H;Masumori N;Tsukamoto T;Sato N;田中俊明
- 通讯作者:田中俊明
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TANAKA Toshiaki其他文献
TANAKA Toshiaki的其他文献
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