Regulation of the Notch target gene Hes-1 by TGFalpha induced Ras/MAPK signaling in human neuroblastoma cells.
(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:
https://lup.lub.lu.se/record/142569
- author
- Stockhausen, Marie LU ; Sjölund, Jonas LU and Axelson, Håkan LU
- organization
- publishing date
- 2005
- 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}}, }