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

Summary, in English

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: Marie Stockhausen; Jonas Sjölund; Håkan Axelson
• Department/s: Department of Translational Medicine
• Publishing year: 2005
• Language: English
• Pages: 218-228
• Publication/Series: Experimental Cell Research
• Volume: 310
• Issue: Aug 22
• Links: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16120441&dopt=Abstract; http://dx.doi.org/10.1016/j.yexcr.2005.07.011
• Document type: Journal article
• Publisher: Academic Press
• Topic: Cancer and Oncology
• Keywords: neuroblastoma; Notch; TGF alpha; ERK; Hes-1; Ras/MAPK signaling; Hash-1
• Status: Published
• ISBN/ISSN/Other: ISSN: 1090-2422