期刊
ONCOGENE
卷 28, 期 36, 页码 3188-3196出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2009.171
关键词
AEG-1; FOXO1; p27(Kip1); p21(Cip1); Akt; breast cancer
资金
- Ministry of Science and Technology of China [2005CB724605]
- Foundation of Ministry of Science and Technology of China [30670803, 30770836, 30771110, 30870963, 30831160517, 30872930]
- Program for New Century Excellent Talents in University [NCET-07-0877]
- Science and Technology Department of Guangdong Province, China [07001503, 8251008901000006, 2008A030201006]
- Foundation of Ministry of Education [(2008) 890, 200805580047]
- Science and Technology Department of Guangdong Province, Zhuhai City [PC20071076]
- Guangdong Provincial Natural Science Foundation [2006Z3-E4081]
- 985-II project
We have previously reported that astrocyte elevated gene-1 (AEG-1) was upregulated in human breast cancer. However, the biological function of AEG-1 in the development and progression of breast cancer remains to be clarified. In this study, we examined the effect of AEG-1 on cell proliferation and found that AEG-1 upregulation was significantly linked to increased Ki67 (P < 0.001). Ectopic expression of AEG-1 in MCF-7 and MDA-MB-435 breast cancer cells dramatically enhanced cell proliferation and their ability of anchorage-independent growth, whereas silencing endogenous AEG-1 with shRNAs inhibited cell proliferation and colony-forming ability of the cells on soft agar. Furthermore, these proliferative effects were significantly associated with decreases of p27(Kip1) and p21(Cip1) two key cell-cycle inhibitors. Moreover, we further demonstrated that AEG-1 could downregulate the transcriptional activity of FOXO1 by inducing its phosphorylation through the PI3K/Akt signaling pathway. These observations were further confirmed in clinical human primary breast cancer specimens, in which high-level expression of AEG-1 was inversely correlated with the expression of FOXO1. Taken together, our results provide the first demonstration of a novel mechanism by which AEG-1 induces proliferation of breast cancer cell, and our findings suggest that AEG-1 might play an important role in tumorigenesis of breast cancer. Oncogene (2009) 28, 3188-3196; doi: 10.1038/onc.2009.171; published online 27 July 2009
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