Regulation of the Notch target gene Hes-1 by TGF{alpha} induced Ras/MAPK signaling in human neuroblastoma cells
- Department of Laboratory Medicine, Division of Molecular Medicine, Lund University, University Hospital MAS, Entrance 78, S-205 02 Malmoe (Sweden)
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 up-regulation 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.
- OSTI ID:
- 20717671
- Journal Information:
- Experimental Cell Research, Vol. 310, Issue 1; Other Information: DOI: 10.1016/j.yexcr.2005.07.011; PII: S0014-4827(05)00347-2; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0014-4827
- Country of Publication:
- United States
- Language:
- English
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