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学科主题临床医学
Thromboxane A2 receptor a promotes tumor growth through an autoregulatory feedback pathway
Huang, Run-Yue1,2; Li, Ming-Yue1; Ng, Calvin S. H.1; Wan, Innes Y. P.1; Kong, Angel W. Y.1; Du, Jing3; Long, Xiang3; Underwood, Malcolm J.1; Mok, Tony S. K.4; Chen, George G.1
关键词thromboxane synthase thromboxane A2 receptor autoregulation cancer smoking lung
刊名JOURNAL OF MOLECULAR CELL BIOLOGY
2013-12-01
DOI10.1093/jmcb/mjt038
5期:6页:380-390
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Cell Biology
研究领域[WOS]Cell Biology
关键词[WOS]CELL LUNG-CANCER ; CIGARETTE-SMOKING ; DOWN-REGULATION ; BLADDER-CANCER ; UP-REGULATION ; EXPRESSION ; A(2) ; CYCLOOXYGENASE-2 ; OVEREXPRESSION ; ACTIVATION
英文摘要

Tobacco smoking can cause a number of cancers. The role of thromboxane synthase (TxAS) in smoking-related cancers is largely unknown. In this study, 37 pairs of tumor and non-tumor lung tissues of non-small-cell lung cancer, 5 lung cancer cell lines, and a mouse tumor model were used to study TxAS and its related molecules. A mouse model of smoking carcinogen 4-methylnitrosamino-1-3-pyridyl-1-butanone (NNK)-induced lung tumor showed an increase in TxAS. Thromboxane A2 receptor (TP) was aberrant in lung cancer tissues of smokers. TxAS and TP were increased in lung tissues of NNK-treated mice. The in vitro studies showed that TP alpha rather than TP beta promoted tumor growth, and NNK increased TP alpha. NNK-induced TxAS, which depended on activation of cyclooxygenase-2 (COX-2), ERK and NF-kappa B, could be inhibited by miR-34b/c. TP alpha played a positive role in NNK-induced COX-2/ERK/NF-kappa B activation, leading to the upregulation of TxAS expression and thromboxane A2 (TxA2) synthesis. The newly synthesized TxA2 could further activate TP alpha, forming an autoregulatory feedback loop for TP alpha activation. Collectively, NNK promotes lung tumor growth via inducing TxAS and TP alpha, which constitutes an auto-positive feedback loop to exaggerate the growth. This study suggests that TP alpha and TxAS are the ideal targets against smoking-related lung cancer.

语种英语
WOS记录号WOS:000330715900004
项目编号CUHK475211
资助机构Research Grants Council of the Hong Kong SAR
引用统计
被引频次:15[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/62412
专题北京大学深圳医院
作者单位1.Peking Univ, Shenzhen Hosp, Shenzhen 518036, Peoples R China
2.Chinese Univ Hong Kong, Prince Wales Hosp, Dept Surg, Shatin, Hong Kong, Peoples R China
3.Guangzhou Univ Chinese Med, Affiliated Hosp 2, Guangzhou 510006, Guangdong, Peoples R China
4.Chinese Univ Hong Kong, Prince Wales Hosp, Dept Clin Oncol, Shatin, Hong Kong, Peoples R China
推荐引用方式
GB/T 7714
Huang, Run-Yue,Li, Ming-Yue,Ng, Calvin S. H.,et al. Thromboxane A2 receptor a promotes tumor growth through an autoregulatory feedback pathway[J]. JOURNAL OF MOLECULAR CELL BIOLOGY,2013,5(6):380-390.
APA Huang, Run-Yue.,Li, Ming-Yue.,Ng, Calvin S. H..,Wan, Innes Y. P..,Kong, Angel W. Y..,...&Chen, George G..(2013).Thromboxane A2 receptor a promotes tumor growth through an autoregulatory feedback pathway.JOURNAL OF MOLECULAR CELL BIOLOGY,5(6),380-390.
MLA Huang, Run-Yue,et al."Thromboxane A2 receptor a promotes tumor growth through an autoregulatory feedback pathway".JOURNAL OF MOLECULAR CELL BIOLOGY 5.6(2013):380-390.
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