Journal
LUNG CANCER
Volume 77, Issue 1, Pages 24-30Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.lungcan.2012.02.015
Keywords
Bmi-1; shRNA; Lung adenocarcinoma; Metastasis; Migration; Inhibit
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Funding
- Liaoning Provincial Funding of Natural Scinces [20072169]
- Dalian Municipal Science and Technology Fund [2008E11SF162]
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Bmi-1 has been implicated in cancer cell growth and metastasis in a variety of tumor types. In this study, we sought to evaluate the expression of Bmi-1 in lung adenocarcinoma samples, and to determine if a correlation exists between Bmi-1 expression and clinical features of lung cancer, such as metastasis. Our results showed that Bmi-1 expression is increased in lung cancer tissues compared to adjacent non-cancerous tissues, and is associated with clinical features of lung cancer, including clinical stage and distant metastasis. We were then interested in determining if shRNA-mediated knockdown of Bmi-1 would inhibit metastasis of lung adenocarcinoma cells. To this end, we chose the most efficient shRNA duplexes targeting Bmi-1, and constructed two stably transfected lung adenocarcinoma cell lines (A549 and SPCA1). The shRNA-mediated knockdown of Bmi-1 significantly reduced migration in vitro, and metastasis in vivo, of A549 and SPCA1 cells. More importantly, knockdown of Bmi-1 also upregulated PTEN expression, and downregulated p-Akt and VEGF expression. These data support the hypothesis that Bmi-1 regulates key pathways involved in the metastasis of lung adenocarcinoma cells. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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