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Prolyl Hydroxylase-3 Is Down-regulated in Colorectal Cancer Cells and Inhibits IKK beta Independent of Hydroxylase Activity
文献类型：期刊论文
| 作者 | Xue, Jing; Li, Xuebing; Jiao, Shi; Wei, Ye; Wu, Guohao; Fang, Jing（方靖） |
| 刊名 | GASTROENTEROLOGY
 |
| 出版日期 | 2010 |
| 卷号 | 138期号:2页码:606-615 |
| 通讯作者 | Fang, J (reprint author), Chinese Acad Sci, Inst Nutr Sci, SIBS, Key Lab Nutr & Metab, 294 Taiyuan Rd, Shanghai 200031, Peoples R China. |
| 英文摘要 | BACKGROUND & AIMS: Prolyl hydroxylase (PHD) hydroxylates hypoxia inducible factor (HIF) alpha, leading to HIF alpha degradation. The PHD family comprises PHD1, PHD2, and PHD3. The enzymatic activity of PHDs is O(2)-dependent, so PHDs are believed to be oxygen sensors as well as tumor suppressors. However, the expression pattern of PHDs in colorectal cancer and the correlation between their expression level and tumorigenesis is unclear. METHODS: We determined the expression of PHDs in 60 human primary colorectal carcinoma tissues, paired with normal colorectal tissues. PHD3 expression levels were knocked down using small interfering RNA (siRNA); cells were analyzed by immunoblotting, immunoprecipitation, and histochemical analyses. In vivo tumor growth was analyzed in nu/nu mice. RESULTS: Expression of PHD3 is decreased in colorectal cancer tissues. Decreased expression of PHD3 is associated with higher tumor grade and metastasis. PHD3 inhibits phosphorylation of inhibitor of kappa B (I kappa B) kinase (IKK) beta and activation of (NF) kappa B, independent of its hydroxylase activity. PHD3 associates with IKK beta but does not target it for destruction; instead, PHD3 blocks the interaction between IKK beta and Hsp90 that is required for phosphorylation of IKK beta. Knockdown of PHD3 increased resistance of colorectal cancer cells to the effects of tumor necrosis factor-alpha and tumorigenesis. CONCLUSIONS: PHD3 appears to be a tumor suppressor in colorectal cancer cells that inhibits IKK beta/NF-kappa B signaling, independent of its hydroxylase activity. Activation of NF-kappa B has been observed in colon cancer. Determination of PHD3 status could aid targeted therapy selection for patients with colorectal tumors that have increased NF-kappa B activity. |
| 类目[WOS] | Gastroenterology & Hepatology |
| 研究领域[WOS] | Gastroenterology & Hepatology |
| 关键词[WOS] | NF-KAPPA-B ; HYPOXIA-RESPONSIVE ELEMENT ; SIGNALING PATHWAYS ; DOMAIN PROTEINS ; OXYGEN SENSOR ; HIF-ALPHA ; TNF-ALPHA ; KINASE ; INFLAMMATION ; ACTIVATION |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000274300900028 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/348]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所_营养与癌症研究组 |
| 推荐引用方式 GB/T 7714 | Xue, Jing,Li, Xuebing,Jiao, Shi,et al. Prolyl Hydroxylase-3 Is Down-regulated in Colorectal Cancer Cells and Inhibits IKK beta Independent of Hydroxylase Activity[J]. GASTROENTEROLOGY,2010,138(2):606-615. |
| APA | Xue, Jing,Li, Xuebing,Jiao, Shi,Wei, Ye,Wu, Guohao,&Fang, Jing.(2010).Prolyl Hydroxylase-3 Is Down-regulated in Colorectal Cancer Cells and Inhibits IKK beta Independent of Hydroxylase Activity.GASTROENTEROLOGY,138(2),606-615. |
| MLA | Xue, Jing,et al."Prolyl Hydroxylase-3 Is Down-regulated in Colorectal Cancer Cells and Inhibits IKK beta Independent of Hydroxylase Activity".GASTROENTEROLOGY 138.2(2010):606-615. |
入库方式： OAI收割
来源：上海营养与健康研究所
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