1. Expression of Concern: HER2 signaling enhances 5′UTR‐mediated translation of c‐Myc mRNA
- Author
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Sylvie Ménard, Clelia Olgiati, Barbara Casati, Patrizia Casalini, Marilena V. Iorio, and Enrico Galmozzi
- Subjects
Regulation of gene expression ,Untranslated region ,Messenger RNA ,Five prime untranslated region ,Physiology ,Clinical Biochemistry ,Cell Biology ,Biology ,Molecular biology ,Wortmannin ,chemistry.chemical_compound ,chemistry ,Protein biosynthesis ,Protein kinase B ,PI3K/AKT/mTOR pathway - Abstract
The increased levels of c-Myc protein observed previously in an ovarian carcinoma cell line stably transfected to express HER2 has suggested a role for the HER2 pathway in c-Myc expression. Analysis of HER2-transfected cells stimulated with heregulin β1 (HRG) revealed increased c-Myc protein levels but not a corresponding increase in c-Myc mRNA expression or any change in c-Myc protein half-life. Transfection of HER2-overexpressing cells with a construct containing the 5′ untranslated region (5′UTR) of c-Myc mRNA originated from the P2 promoter and placed upstream of the Renilla luciferase gene, enhanced reporter expression upon stimulation with HRG. The HRG-mediated increase in reporter activity correlated with the HRG-mediated induction observed for c-Myc protein, identifying the P2-derived leader (P2L) of c-Myc mRNA as the cis-element involved in c-Myc translational induction. Both the increase in c-Myc protein levels and P2L-enhanced translational activity were inhibited by the PI3K inhibitor wortmannin. Together, these results demonstrate that HRG stimulation of HER2 overexpressing cells leads to enhanced c-Myc protein synthesis through activation of the PI3K/Akt/mTOR pathway and that the P2L of c-Myc mRNA is the element responsible for induction of c-Myc translation. © 2004 Wiley-Liss, Inc.
- Published
- 2004
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