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

Författare

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.

Publiceringsår

2005

Språk

Engelska

Sidor

218-228

Publikation/Tidskrift/Serie

Experimental Cell Research

Volym

310

Issue

Aug 22

Dokumenttyp

Artikel i tidskrift

Förlag

Academic Press

Ämne

  • Cancer and Oncology

Nyckelord

  • neuroblastoma
  • Notch
  • TGF alpha
  • ERK
  • Hes-1
  • Ras/MAPK signaling
  • Hash-1

Status

Published

ISBN/ISSN/Övrigt

  • ISSN: 1090-2422