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ErbB2/Her‐2 regulates the expression of Akt2 in prostate cancer cells
Author(s) -
Le Page Cécile,
Koumakpayi Ismaël Hervé,
Péant Benjamin,
Delvoye Nathalie,
Saad Fred,
MesMasson AnneMarie
Publication year - 2011
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.21483
Subject(s) - akt2 , du145 , lncap , prostate cancer , protein kinase b , cancer research , blot , gene silencing , biology , signal transduction , cancer , microbiology and biotechnology , medicine , akt1 , gene , biochemistry
Abstract BACKGROUND We have previously reported that ErbB family members regulate the signaling pathway leading to Akt and NF‐kappaB activation in prostate cancer cells. In this study, the regulation of Akt2 expression in LNCaP, DU145, and PC‐3 prostate cancer cell lines was investigated. METHODS Akt‐2 expression was analyzed by western‐blotting and Q‐PCR in cell lines. We also analyzed the Akt‐2 protein expression in a tissue microarray from 64 prostate cancer patients. Akt‐2 promoter activity was assessed and analyzed by luciferase assay. RESULTS A concomitant over‐expression of Her‐2 and Akt2 expression was observed by western‐blotting and quantitative‐PCR in prostate cancer cell lines. A significant correlation between Her‐2 and Akt2 protein expression was also observed by immunohistochemistry assay on prostate cancer tissues. In LNCaP cells, over‐expression of Akt2 protein and mRNA was decreased by Her‐2 pharmacologic inhibitors as well as small interfering RNA (siRNA) specific to Her‐2 . Cloning of the AKT2 promoter in a luciferase reporter plasmid further showed that Akt2 over‐expression in cell lines is associated with increased AKT2 promoter activity suggesting that Her‐2 modulates a signaling pathway involving AKT2 gene regulation. CONCLUSION This study reveals a novel mechanism of Akt2 regulation in prostate cancer cells. Prostate 72:777–788, 2012. © 2011 Wiley Periodicals, Inc.