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Regulation of the Notch target gene Hes-1 by TGFalpha induced Ras/MAPK signaling in human neuroblastoma cells.

Stockhausen, Marie LU ; Sjölund, Jonas LU and Axelson, Håkan LU (2005) In Experimental Cell Research 310(Aug 22). p.218-228
Abstract
Ras and Notch signaling have recently been shown to cooperate in the maintenance of neoplastic transformation. Here, we show that TGF alpha, a known activator of Ras signaling, can drive cell proliferation and at the same time induce the expression of the Notch target Hes-1 in the neuroblastoma cell line SK-N-BE(2)c. The up-regulation of Hes-1 occurred both at the transcriptional and protein levels and by use of EGFR and MEK inhibitors we could show that the Hes-1 response was dependent on activation of the MAP kinase ERK. Blocking Notch activation by gamma-secretase inhibition did not profoundly affect the Hes-1 levels, neither in untreated nor in TGF alpha treated cells. The upregulation of Hes-1 was associated with down-regulation of... (More)
Ras and Notch signaling have recently been shown to cooperate in the maintenance of neoplastic transformation. Here, we show that TGF alpha, a known activator of Ras signaling, can drive cell proliferation and at the same time induce the expression of the Notch target Hes-1 in the neuroblastoma cell line SK-N-BE(2)c. The up-regulation of Hes-1 occurred both at the transcriptional and protein levels and by use of EGFR and MEK inhibitors we could show that the Hes-1 response was dependent on activation of the MAP kinase ERK. Blocking Notch activation by gamma-secretase inhibition did not profoundly affect the Hes-1 levels, neither in untreated nor in TGF alpha treated cells. The upregulation of Hes-1 was associated with down-regulation of its pro-neuronal target gene Hash-1. Taken together, these results show that TGF alpha is a potent mitogen of neuroblastoma cells and suggest a connection between activation of ERK and Hes-1, thus providing a link between the Ras and Notch signaling pathways. (Less)
Please use this url to cite or link to this publication:
author
; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
neuroblastoma, Notch, TGF alpha, ERK, Hes-1, Ras/MAPK signaling, Hash-1
in
Experimental Cell Research
volume
310
issue
Aug 22
pages
218 - 228
publisher
Academic Press
external identifiers
  • wos:000232511000021
  • pmid:16120441
  • scopus:25844517958
ISSN
1090-2422
DOI
10.1016/j.yexcr.2005.07.011
language
English
LU publication?
yes
id
01b297a6-fb9a-45a3-bda6-4b75ddf5ebd1 (old id 142569)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16120441&dopt=Abstract
date added to LUP
2016-04-01 12:12:07
date last changed
2022-03-28 21:40:25
@article{01b297a6-fb9a-45a3-bda6-4b75ddf5ebd1,
  abstract     = {{Ras and Notch signaling have recently been shown to cooperate in the maintenance of neoplastic transformation. Here, we show that TGF alpha, a known activator of Ras signaling, can drive cell proliferation and at the same time induce the expression of the Notch target Hes-1 in the neuroblastoma cell line SK-N-BE(2)c. The up-regulation of Hes-1 occurred both at the transcriptional and protein levels and by use of EGFR and MEK inhibitors we could show that the Hes-1 response was dependent on activation of the MAP kinase ERK. Blocking Notch activation by gamma-secretase inhibition did not profoundly affect the Hes-1 levels, neither in untreated nor in TGF alpha treated cells. The upregulation of Hes-1 was associated with down-regulation of its pro-neuronal target gene Hash-1. Taken together, these results show that TGF alpha is a potent mitogen of neuroblastoma cells and suggest a connection between activation of ERK and Hes-1, thus providing a link between the Ras and Notch signaling pathways.}},
  author       = {{Stockhausen, Marie and Sjölund, Jonas and Axelson, Håkan}},
  issn         = {{1090-2422}},
  keywords     = {{neuroblastoma; Notch; TGF alpha; ERK; Hes-1; Ras/MAPK signaling; Hash-1}},
  language     = {{eng}},
  number       = {{Aug 22}},
  pages        = {{218--228}},
  publisher    = {{Academic Press}},
  series       = {{Experimental Cell Research}},
  title        = {{Regulation of the Notch target gene Hes-1 by TGFalpha induced Ras/MAPK signaling in human neuroblastoma cells.}},
  url          = {{http://dx.doi.org/10.1016/j.yexcr.2005.07.011}},
  doi          = {{10.1016/j.yexcr.2005.07.011}},
  volume       = {{310}},
  year         = {{2005}},
}