Publication in refereed journal
香港中文大学研究人员 ( 现职)
| 尹怀信教授 (耳鼻咽喉-头颈外科学系) |
| Professor VLANTIS Alexander Chris (耳鼻咽喉-头颈外科学系) |
| 陈功教授 (外科学系) |
全文
| 数位物件识别号 (DOI) http://dx.doi.org/10.1002/jcb.20157 |
引用次数
Web of Sciencehttp://aims.cuhk.edu.hk/converis/portal/Publication/51WOS source URL
其它资讯
摘要Heme oxygenase-1 (HO-1) plays a role in the resistance to apoptosis of several types of cells, but its role in the development of thyroid cancer is unknown. In this study, we investigated the regulation of HO-1 in human papillary thyroid carcinoma cells (KAT5). The results show that HO-1 is significantly induced by hemin and cadmium. In addition to inducing HO-1, hemin and cadmium also cause a rise in the levels of p21, a cyclin-dependent kinase inhibitor. Cells with increased levels of HO-1 and p21 were more resistant to apoptotic stimuli than cells with normal levels. The cells resistant to apoptosis also displayed an increased arrest at the G(0)/G(1) phase of the cell-cycle. The induced levels of HO-1 and p21 were significantly reduced by p38 mitogen-activated protein kinase (p38 MAPK) and extracellular-regulated kinase (ERK) inhibitors. More importantly, KAT5 cells regained their sensitivity to apoptotic stimuli after they were treated with these kinase inhibitors, indicating that p38 MAPK and ERK are required for the resistance to apoptosis conferred by HO-1. Furthermore, we demonstrated that increased levels of HO-1 and p21 expression are associated with an increase in the activity of NF-kappaB and that inhibiting NF-kappaB leads to a block in the induction of HO-1 and p21. In summary, this study reveals that an increase in the level of HO-1 markedly reduces the sensitivity of papillary thyroid carcinoma cells to apoptotic stimuli. The HO-1 pathway of apoptosis resistance is associated with an increase in the levels of p21, involves a p38 MAPK and ERK-mediated mechanism and can be suppressed by inhibiting NF-kappaB.
着者Chen GG, Liu ZM, Vlantis AC, Tse GMK, Leung BCH, van Hasselt CA
期刊名称Journal of Cellular Biochemistry
出版年份2004
月份8
日期15
卷号92
期次6
出版社WILEY-LISS
页次1246 - 1256
国际标準期刊号0730-2312
电子国际标準期刊号1097-4644
语言英式英语
关键词apoptosis; heme oxygenase-1; p21; thyroid cancer
Web of Science 学科类别Biochemistry & Molecular Biology; BIOCHEMISTRY & MOLECULAR BIOLOGY; Cell Biology; CELL BIOLOGY
