Bmi-1 promotes invasion and metastasis, and its elevated expression is correlated with an advanced stage of breast cancer

Molecular Cancer

Research

Rong Zhang¹  Hsiang-Fu Kung²  Mu-Sheng Zeng³  Li-Bing Song³  Li-Hua Xu³  Man-Zhi Li³  Yan Feng³  Bao-Hong Guo⁴ 

[1] Department of Endoscopy and Laser treatment, Sun Yat-Sen University Cancer Center, Guangzhou, PR China;Stanley Ho Centre for Emerging Infectious Diseases, School of Public Health and Primary Care, Prince of Wales Hospital, the Chinese University of Hong Kong, Shatin, N.T., Hong Kong, PR China;State Key Laboratory of Oncology in South China and Department of Experimental Research, Sun Yat-Sen University Cancer Center, Guangzhou, PR China;State Key Laboratory of Oncology in South China and Department of Experimental Research, Sun Yat-Sen University Cancer Center, Guangzhou, PR China;Stanley Ho Centre for Emerging Infectious Diseases, School of Public Health and Primary Care, Prince of Wales Hospital, the Chinese University of Hong Kong, Shatin, N.T., Hong Kong, PR China;

关键词: Breast Cancer;    Breast Cancer Tissue;    Advanced Clinical Stage;    High Expression Group;    Primary Cancer Tissue;   

DOI  :  10.1186/1476-4598-10-10

 received in 2010-04-09, accepted in 2011-01-28,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundB-lymphoma Moloney murine leukemia virus insertion region-1 (Bmi-1) acts as an oncogene in various tumors, and its overexpression correlates with a poor outcome in several human cancers. Ectopic expression of Bmi-1 can induce epithelial-mesenchymal transition (EMT) and enhance the motility and invasiveness of human nasopharyngeal epithelial cells (NPECs), whereas silencing endogenous Bmi-1 expression can reverse EMT and reduce the metastatic potential of nasopharyngeal cancer cells (NPCs). Mouse xenograft studies indicate that coexpression of Bmi-1 and H-Ras in breast cancer cells can induce an aggressive and metastatic phenotype with an unusual occurrence of brain metastasis; although, Bmi-1 overexpression did not result in oncogenic transformation of MCF-10A cells. However, the underlying molecular mechanism of Bmi-1-mediated progression and the metastasis of breast cancer are not fully elucidated at this time.ResultsBmi-1 expression is more pronouncedly increased in primary cancer tissues compared to matched adjacent non-cancerous tissues. High Bmi-1 expression is correlated with advanced clinicopathologic classifications (T, N, and M) and clinical stages. Furthermore, a high level of Bmi-1 indicates an unfavorable overall survival and serves as a high risk marker for breast cancer. In addition, inverse transcriptional expression levels of Bmi-1 and E-cadherin are detected between the primary cancer tissues and the matched adjacent non-cancerous tissues. Higher Bmi-1 levels are found in the cancer tissue, whereas the paired adjacent non-cancer tissue shows higher E-cadherin levels. Overexpression of Bmi-1 increases the motility and invasive properties of immortalized human mammary epithelial cells, which is concurrent with the increased expression of mesenchymal markers, the decreased expression of epithelial markers, the stabilization of Snail and the dysregulation of the Akt/GSK3β pathway. Consistent with these observations, the repression of Bmi-1 in highly metastatic breast cancer cells remarkably reduces cellular motility, invasion and transformation, as well as tumorigenesis and lung metastases in nude mice. In addition, the repression of Bmi-1 reverses the expression of EMT markers and inhibits the Akt/GSK3β/Snail pathway.ConclusionsThis study demonstrates that Bmi-1 promotes the invasion and metastasis of human breast cancer and predicts poor survival.

【 授权许可】

Unknown   
© Guo et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.