期刊
INTERNATIONAL JOURNAL OF CANCER
卷 125, 期 11, 页码 2511-2519出版社
WILEY
DOI: 10.1002/ijc.24588
关键词
p21-activated kinase 1; gastric cancer; cell proliferation; cyclin B1; NF-kappa B
类别
资金
- National Natural Science Foundation of China [30370736, 30570966, 90813038]
- Doctoral Fund of Ministry of Education of China [20050159023]
p21-activated kinase 1 (Pak1), a serine/threonine kinase, has been implicated in cytoskeletal remodelling, cell motility, apoptosis and transformation. However, the role of Pak1 in gastric cancer remains unclear. In this study, we detected Pak1 expression in gastric cancer tissues from 40 patients by western blot. Overexpression of Pak1 was associated with progression, metastasis and prognosis of gastric cancer. In addition, we found that knockdown of Pak1 expression significantly inhibited anchorage-dependent and anchorage-independent growth in gastric cancer cells, and markedly inhibited gastric cancer cell xenograft tumor growth. In further study, data showed that Pak1 could regulate the expression of cyclin B1 at the mRNA and protein levels, and impact the subcellular distribution and the promoter activity of cyclin B1. Results from deletion and mutant analysis supplied a new NF-kappa B binding sites at position -321 of cyclin B1 promoter, and indicated that Pak1 regulated the transcription of cyclin B1 in gastric cancer through NF-kappa B. In conclusion, Pak1 may be a potential prognostic marker and therapeutic target in gastric cancer. (c) 2009 UICC
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