PMID- 15137060
OWN - NLM
STAT- MEDLINE
DCOM- 20040702
LR  - 20211203
IS  - 0021-9541 (Print)
IS  - 0021-9541 (Linking)
VI  - 200
IP  - 1
DP  - 2004 Jul
TI  - HER2 signaling enhances 5'UTR-mediated translation of c-Myc mRNA.
PG  - 82-8
AB  - 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 beta1 (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.
CI  - Copyright 2004 Wiley-Liss, Inc.
FAU - Galmozzi, Enrico
AU  - Galmozzi E
AD  - Molecular Targeting Unit, Department of Experimental Oncology, Istituto Nazionale 
      Tumori, Milan, Italy.
FAU - Casalini, Patrizia
AU  - Casalini P
FAU - Iorio, Marilena Valeria
AU  - Iorio MV
FAU - Casati, Barbara
AU  - Casati B
FAU - Olgiati, Clelia
AU  - Olgiati C
FAU - Menard, Sylvie
AU  - Menard S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (5' Untranslated Regions)
RN  - 0 (Androstadienes)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Neuregulin-1)
RN  - 0 (Protein Synthesis Inhibitors)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins c-myc)
RN  - 0 (RNA, Messenger)
RN  - 155646-83-6 (heregulin beta1)
RN  - 1CC1JFE158 (Dactinomycin)
RN  - 98600C0908 (Cycloheximide)
RN  - EC 1.13.12.- (Luciferases)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (AKT1 protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - XVA4O219QW (Wortmannin)
SB  - IM
ECI - J Cell Physiol. 2021 Sep;236(9):6772. PMID: 34160080
MH  - 5' Untranslated Regions/*metabolism
MH  - Androstadienes/pharmacology
MH  - Carcinoma/genetics/metabolism/pathology
MH  - Cell Line, Tumor
MH  - Clone Cells
MH  - Cycloheximide/pharmacology
MH  - Dactinomycin/pharmacology
MH  - Enzyme Inhibitors/pharmacology
MH  - Female
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Genes, Reporter
MH  - Genes, erbB-2
MH  - Genes, myc/*drug effects
MH  - Humans
MH  - Luciferases/metabolism
MH  - Neuregulin-1/*metabolism/pharmacology
MH  - Ovarian Neoplasms/genetics/metabolism/pathology
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Promoter Regions, Genetic
MH  - *Protein Biosynthesis/drug effects
MH  - Protein Kinases/metabolism
MH  - *Protein Serine-Threonine Kinases
MH  - Protein Synthesis Inhibitors/pharmacology
MH  - Proto-Oncogene Proteins/metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - Proto-Oncogene Proteins c-myc/*biosynthesis/genetics
MH  - RNA, Messenger/*genetics/metabolism
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases
MH  - Wortmannin
EDAT- 2004/05/12 05:00
MHDA- 2004/07/03 05:00
CRDT- 2004/05/12 05:00
PHST- 2004/05/12 05:00 [pubmed]
PHST- 2004/07/03 05:00 [medline]
PHST- 2004/05/12 05:00 [entrez]
AID - 10.1002/jcp.20012 [doi]
PST - ppublish
SO  - J Cell Physiol. 2004 Jul;200(1):82-8. doi: 10.1002/jcp.20012.