Publication in refereed journal
香港中文大学研究人员 ( 现职)
| 陈功教授 (外科学系) |
| 莫树锦教授 (肿瘤学系) |
| Professor Malcolm John UNDERWOOD (外科学系) |
| 江颖欣小姐 (外科学系) |
| 吴士衡教授 (外科学系) |
| 李明月教授 (外科学系) |
全文
| 数位物件识别号 (DOI) http://dx.doi.org/10.1093/jmcb/mjt038 |
引用次数
Web of Sciencehttp://aims.cuhk.edu.hk/converis/portal/Publication/13WOS source URL
其它资讯
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.
着者Huang RY, Li MY, Ng CSH, Wan IYP, Kong AWY, Du J, Long X, Underwood MJ, Mok TSK, Chen GG
期刊名称Journal of Molecular Cell Biology
出版年份20http://aims.cuhk.edu.hk/converis/portal/Publication/13
月份12
日期1
卷号5
期次6
出版社OXFORD UNIV PRESS
页次380 - 390
国际标準期刊号1674-2788
电子国际标準期刊号1759-4685
语言英式英语
关键词autoregulation; cancer; lung; smoking; thromboxane A2 receptor; thromboxane synthase
Web of Science 学科类别Cell Biology; CELL BIOLOGY
