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：
TANAKA Toshiaki
金额：
$ 2.16万
依托单位：
Sapporo Medical University
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

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)、SMKT-R2和SMKT-R3的VHL基因突变细胞系稳定过表达PHD3。在 Caki-1（一种 VHL 野生型 RCC 细胞系）中，PHD3 表达在非汇合状态下被诱导。在 Caki-1 中，在非汇合状态下，PI3K/Akt/mTOR 通路被激活，用 LY294002 抑制该通路可降低 PHD3 表达。即使在 HIF-1a/2a 双敲低 Caki-1 中，PI3k/Akt/mTOR 途径的激活也会诱导 PHD3 的过度表达。此外，与对照 siRNA 相比，PHD3 siRNA 在 Caki-1 中促进细胞增殖，但不诱导 HIF 蛋白表达。即使在VHL突变体SMKT-R2和SMKT-R3中，PHD3 siRNA也显示出相同的效果。另一方面，将表达PHD3的质粒转染至常氧下不表达PHD3的RCC细胞系ACHN中，与空载体转染相比，细胞增殖减少。在22例RCC患者中，术前血清抗PHD3抗体滴度显着升高RCC 患者的情况高于健康志愿者。术前和术后血清样本均在肿瘤切除后至少 1 个月从 17 名患者身上采集。所有17例患者手术切除后血清抗PHD3滴度均较术前下降。结果表明，抗PHD3抗体可能是肾细胞癌的一种新型血清学标志物，其滴度可能反映每个个体的肿瘤负荷。

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）

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.;Tsukamoto; T.
通讯作者：
T.

PHD3 has a HIF-independent-antiproliferative function in renal cell carcinoma

PHD3 在肾细胞癌中具有不依赖 HIF 的抗增殖功能