Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10905426 | Experimental Cell Research | 2005 | 11 Pages |
Abstract
Ras and Notch signaling have recently been shown to cooperate in the maintenance of neoplastic transformation. Here, we show that TGFα, 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 γ-secretase inhibition did not profoundly affect the Hes-1 levels, neither in untreated nor in TGFα 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 TGFα 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.
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Authors
Marie-Thérése Stockhausen, Jonas Sjölund, HÃ¥kan Axelson,