PMID- 10216954
OWN - NLM
STAT- MEDLINE
DCOM- 19990517
LR  - 20191210
IS  - 1357-2725 (Print)
IS  - 1357-2725 (Linking)
VI  - 31
IP  - 1
DP  - 1999 Jan
TI  - Cell type-dependent and -independent control of HER-2/neu translation.
PG  - 201-13
AB  - Overexpression of the HER-2 oncogene occurs in a variety of human tumors,
      including 25-30% of breast carcinomas, and has been associated with an adverse
      prognosis. Amplification of the HER-2 gene is frequently detected in tumors, but 
      by itself may not fully account for HER-2 overexpression since transcriptional
      and post-transcriptional mechanisms also regulate HER-2 protein synthesis. Our
      studies reveal that the efficiency of HER-2 translation differs between primary
      and transformed cells. In primary human fibroblasts and human mammary epithelial 
      cells, the HER-2 mRNA is associated with monosome and small polysome fractions.
      In contrast, in BT474 and MCF-7 human breast cancer cell lines and in COS-7 cells
      the mRNA co-sedimented with larger polysomes, indicating that it is more
      efficiently translated in these transformed cells. Northern analysis revealed no 
      detectable mRNA size difference, and nuclease S1 protection and sequence analyses
      showed no differences between the HER-2 transcript leader in primary cells
      compared to transformed human cells. The transcript leader in all cell types
      contains a short upstream open reading frame that is also conserved in other
      mammalian species. Transient transfection assays revealed that the HER-2
      transcript leader repressed downstream translation approximately five-fold in
      both primary and transformed cells and mutation of the upstream initiation codon 
      alleviated most of the inhibitory effect. These results indicate that HER2
      expression is translationally controlled both by a short upstream open reading
      frame that represses HER-2 translation in a cell type-independent manner, and by 
      a distinct cell type-dependent mechanism that increases translational efficiency 
      of HER-2 in transformed cells.
FAU - Child, S J
AU  - Child SJ
AD  - Division of Molecular Medicine, Fred Hutchinson Cancer Research Center, Seattle, 
      WA 98109-1024, USA.
FAU - Miller, M K
AU  - Miller MK
FAU - Geballe, A P
AU  - Geballe AP
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - Netherlands
TA  - Int J Biochem Cell Biol
JT  - The international journal of biochemistry & cell biology
JID - 9508482
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
EIN - Int J Biochem Cell Biol 1999 Aug;31(8):883-4
MH  - Animals
MH  - Base Sequence
MH  - COS Cells/metabolism
MH  - Cell Line, Transformed
MH  - Chlorocebus aethiops
MH  - Fibroblasts/metabolism
MH  - Humans
MH  - Molecular Sequence Data
MH  - *Protein Biosynthesis
MH  - Receptor, ErbB-2/chemistry/*genetics/metabolism
MH  - Transcription, Genetic
EDAT- 1999/04/27 00:00
MHDA- 1999/04/27 00:01
CRDT- 1999/04/27 00:00
PHST- 1999/04/27 00:00 [pubmed]
PHST- 1999/04/27 00:01 [medline]
PHST- 1999/04/27 00:00 [entrez]
AID - S1357-2725(98)00068-5 [pii]
AID - 10.1016/s1357-2725(98)00068-5 [doi]
PST - ppublish
SO  - Int J Biochem Cell Biol. 1999 Jan;31(1):201-13. doi:
      10.1016/s1357-2725(98)00068-5.