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Astrocyte elevated gene-1 is a proliferation promoter in breast cancer via suppressing transcriptional factor FOXO1

Oncogene volume 28, pages 3188–3196 (2009)Cite this article

Abstract

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 p27Kip1 and p21Cip1 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.

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Acknowledgements

This study was supported by grants from the Ministry of Science and Technology of China (Grant (973)2005CB724605); the Foundation of Ministry of Science and Technology of China (No. 30670803, 30770836, 30771110, 30870963, 30831160517, 30872930); Program for New Century Excellent Talents in University (Grant No. NCET-07-0877); the Science and Technology Department of Guangdong Province, China (No. 07001503, 8251008901000006, 2008A030201006); Foundation of Ministry of Education (No. (2008)890 and No. 200805580047); the Science and Technology Department of Guangdong Province, Zhuhai City (PC20071076); Guangdong Provincial Natural Science Foundation (Grant 2006Z3-E4081) and a key grant from the 985-II project.

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  1. J Li, L Yang and L Song: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China

    J Li, X Yan & J Yuan

  2. Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou, Guangdong, China

    J Li, L Yang, H Xiong, L Wang, X Yan, J Yuan, J Wu & M Li

  3. Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China

    L Yang, H Xiong, L Wang, J Wu & M Li

  4. State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China

    L Song

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Correspondence to M Li.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Li, J., Yang, L., Song, L. et al. Astrocyte elevated gene-1 is a proliferation promoter in breast cancer via suppressing transcriptional factor FOXO1. Oncogene 28, 3188–3196 (2009). https://doi.org/10.1038/onc.2009.171

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