Advanced

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
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
2007-07-27 10:42:28
date last changed
2017-09-10 03:43:32
@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},
  keyword      = {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},
  volume       = {310},
  year         = {2005},
}