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学科主题: 临床医学
题名:
Thromboxane A2 receptor a promotes tumor growth through an autoregulatory feedback pathway
作者: 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
发表日期: 2013-12-01
DOI: 10.1093/jmcb/mjt038
卷: 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
所属项目编号: CUHK475211
项目资助者: Research Grants Council of the Hong Kong SAR
WOS记录号: WOS:000330715900004
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/62412
Appears in Collections:北京大学深圳医院_期刊论文

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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

Recommended Citation:
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.
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