TNF alpha induces HIF-1 alpha expression through activation of IKK beta

ASIA unversity > 醫學暨健康學院 > 生物科技學系 > 期刊論文 > Item 310904400/8204

請使用永久網址來引用或連結此文件: http://asiair.asia.edu.tw/ir/handle/310904400/8204

題名:	TNF alpha induces HIF-1 alpha expression through activation of IKK beta
作者:	Kuo, HP (Kuo, Hsu-Ping);Lee, DF (Lee, Dung-Fang);Xia, WY (Xia, Weiya);Wei, YK (Wei, Yongkun);Hung, MC (Hung, Mien-Chie)
貢獻者:	Department of Biotechnology
關鍵詞:	Tumor necrosis factor alpha;Hypoxia-inducible factor 1 alpha;I kappa B kinase beta;Vascular endothelial growth factor;Breast cancer
日期:	2009-11
上傳時間:	2010-03-26 02:29:01 (UTC+0)
出版者:	Asia University
摘要:	The transcription factor hypoxia-inducible factor 1 alpha (HIF-1 alpha) is regulated by oxygen availability as well as various inflammatory mediators, including tumor necrosis factor alpha (TNF alpha). Early work suggested that the phosphatidylinositol-3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) signaling pathways are involved in TNF alpha-mediated HIF-1 alpha accumulation and activation under normoxic conditions. Here, we provide evidence showing that I kappa B kinase beta (IKK beta) is required for HIF-1 alpha regulation by TNF alpha. We found that TNF alpha enhances HIF-1 alpha protein expression in various breast cancer cell lines under either normoxic or hypoxia-mimicking conditions, but has little effect on the HIF-1 alpha mRNA level. Increased HIF-1 alpha expression was found in IKK beta stable clones and transient transfectants, and depletion of IKK beta consistently reduced the amount of HIF-1 alpha protein. Treatment of cells with the IKK beta inhibitor Bay 11-7082 reduced the TNF alpha-induced HIF-1 alpha expression, suggesting that IKK beta is required in this signaling pathway. Decreased expression of vascular endothelial growth factor (VEGF), a direct target of HIF-1 alpha, was shown in IKK beta-knockout mouse embryonic fibroblast cells. We further demonstrated a positive correlation between IKK beta and VEGF expression in primary human breast cancer specimens. Our findings indicate that TNF alpha-induced HIF-1 alpha accumulation is IKK beta dependent, and may enable further understanding of the HIF-1 alpha regulation by inflammatory signals. (C) 2009 Elsevier Inc. All rights reserved.
關聯:	BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 389 (4): 640-644
顯示於類別:	[生物科技學系] 期刊論文

文件中的檔案:

檔案	大小	格式	瀏覽次數
20.docx	0Kb	Unknown	435	檢視/開啟
20.docx	20Kb	Unknown	234	檢視/開啟
310904400-8204.doc	35Kb	Microsoft Word	245	檢視/開啟

在ASIAIR中所有的資料項目都受到原著作權保護.

資料載入中.....