Notch-independent regulation of Hes-1 expression by c-Jun N-terminal kinase signaling in human endothelial cells

Christine Curry, Laura L. Reed, Brian J. Nickoloff, Lucio Miele, Kimberly E. Foreman

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Our laboratory has recently demonstrated constitutive activation of the Notch signaling pathway in Kaposi's sarcoma tumor cells. As endothelial cells (EC) are believed to be the progenitor of these tumor cells, this study was designed to examine the effect of Notch activation on normal human EC. Recent reports suggest Notch activation induces EC growth arrest, and that this growth arrest may be linked to the establishment or maintenance of EC quiescence, the phenotype seen in contact-inhibited EC lining the vasculature. To gain further insight into Notch activation and quiescence, we first confirmed that Notch activation induced EC growth arrest. Next, we examined Notch activation in confluent, growth arrested EC (mimicking the cells lining the vasculature). In contrast to previous reports, we found confluent EC possess lower levels of activated Notch compared to proliferating control cells. Interestingly, these cells express elevated levels of Hes-1 protein (an immediate downstream target of Notch signaling) despite decreased Notch activation. Under these conditions, Hes-1 expression was mediated, at least in part, by a Notch-independent mechanism involving c-jun N-terminal protein kinase (JNK) signaling. This is the first report, to our knowledge, that JNK signaling can modulate Hes-1 expression in a Notch-independent manner.

Original languageEnglish (US)
Pages (from-to)842-852
Number of pages11
JournalLaboratory Investigation
Volume86
Issue number8
DOIs
StatePublished - Aug 29 2006
Externally publishedYes

Fingerprint

Mitogen-Activated Protein Kinase 8
Endothelial Cells
Growth
JNK Mitogen-Activated Protein Kinases
Kaposi's Sarcoma
Neoplasms
Proteins
Stem Cells
Maintenance
Phenotype

Keywords

  • Endothelial cells
  • Growth arrest
  • Hes-1
  • JNK
  • Notch
  • Quiescence

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Notch-independent regulation of Hes-1 expression by c-Jun N-terminal kinase signaling in human endothelial cells. / Curry, Christine; Reed, Laura L.; Nickoloff, Brian J.; Miele, Lucio; Foreman, Kimberly E.

In: Laboratory Investigation, Vol. 86, No. 8, 29.08.2006, p. 842-852.

Research output: Contribution to journalArticle

Curry, Christine ; Reed, Laura L. ; Nickoloff, Brian J. ; Miele, Lucio ; Foreman, Kimberly E. / Notch-independent regulation of Hes-1 expression by c-Jun N-terminal kinase signaling in human endothelial cells. In: Laboratory Investigation. 2006 ; Vol. 86, No. 8. pp. 842-852.
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