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RETRACTED ARTICLE: Knockdown of astrocyte-elevated gene-1 inhibits prostate cancer progression through upregulation of FOXO3a activity

This article was retracted on 19 October 2022

This article has been updated


Astrocyte-elevated gene-1 (AEG-1) has been reported to be upregulated in several malignancies and play a critical role in Ha-ras-mediated oncogenesis through the phosphatidylinositol 3-kinase/AKT signaling pathway. However, the role of AEG-1 in prostate cancer (PC) has never been reported. We now show that AEG-1 is overexpressed in clinical PC tissue samples and cultured PC cells compared to benign prostatic hyperplasia tissue samples and normal prostate epithelial cells. Interestingly, AEG-1 knockdown induced cell apoptosis through upregulation of forkhead box (FOXO) 3a activity. This alteration of FOXO3a activity was dependent on reduction of AKT activity in LNCaP and PC-3 cells with high constitutive AKT activity, but not in DU145 cells with low constitutive AKT activity, although AEG-1 knockdown had no impact on phosphatase and tensin homolog expression in these cells. AEG-1 knockdown also attenuated the constitutive activity of the nuclear factor κB (NF-κB) and the activator protein 1 (AP-1) with a corresponding depletion in the expression of NF-κB and AP-1-regulated genes (interleukin (IL)-6, IL-8 and matrix metalloproteinase-9) and significantly decreased cell invasion properties of PC-3 and DU145 cells. Overall, our findings suggest that aberrant AEG-1 expression plays a dominant role as a positive auto-feedback activator of AKT and as a suppressor of FOXO3a in PC cells. AEG-1 may therefore represent a novel genetic biomarker to serve as an attractive molecular target for new anticancer agents to prevent PC cell progression and metastasis.

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Change history



astrocyte-elevated gene-1


activator protein 1


forkhead box






matrix metalloproteinase-9


nuclear factor κB


phosphatidylinositol 3-kinase


phosphorodiamidate morpholino antisense oligonucleotide


phosphatase and tensin homolog


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We thank Dr Roger Erickson for his support and assistance with the preparation of the manuscript. This study was supported by grants RO1CA101844, RO1AG021418, RO1CA108612, RO1CA111470 and T32DK07790 from the NIH, VA REAP award, Merit Review grants and Yamada Science Foundation.

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Correspondence to R Dahiya.

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Kikuno, N., Shiina, H., Urakami, S. et al. RETRACTED ARTICLE: Knockdown of astrocyte-elevated gene-1 inhibits prostate cancer progression through upregulation of FOXO3a activity. Oncogene 26, 7647–7655 (2007).

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