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Inhibition of notch signaling induces neural differentiation in Ewing sarcoma.

Publication ,  Journal Article
Baliko, F; Bright, T; Poon, R; Cohen, B; Egan, SE; Alman, BA
Published in: Am J Pathol
May 2007

Cells from Ewing sarcoma exhibit cellular features and express markers, suggesting that the tumor is of neuroectodermal origin. Because Notch signaling regulates the differentiation of neuroectodermal cells during development, we examined the role of Notch signaling in Ewing sarcomas. We found that Ewing sarcomas express Notch receptors, ligands, and the Notch target gene HES1. To determine the functional implications of Notch signaling, we expressed tetracycline-regulated constitutively active, dominant-negative (DN), or wild-type Notch-1 receptors in two Ewing sarcoma cell lines, or we treated the cell lines with a gamma-secretase inhibitor. Expression of the constitutively active Notch-1 reduced proliferation and expression of the DN Notch-1 reduced apoptosis in vitro. However, there was only a small difference in the volume of tumors that formed when the cell lines expressing these constructs were implanted in nude mice. Xenograft tumors derived from the cell lines expressing DN Notch-1 exhibited a neural phenotype. Treatment with a gamma-secretase inhibitor caused similar changes as expression of the DN construct. Notch signaling plays a role in cell differentiation, proliferation, and apoptosis in Ewing sarcoma, but its inhibition is only associated with a small change in tumor growth potential.

Duke Scholars

Published In

Am J Pathol

DOI

ISSN

0002-9440

Publication Date

May 2007

Volume

170

Issue

5

Start / End Page

1686 / 1694

Location

United States

Related Subject Headings

  • Transfection
  • Signal Transduction
  • Sarcoma, Ewing
  • Reverse Transcriptase Polymerase Chain Reaction
  • Receptors, Notch
  • Pathology
  • Neurons
  • Mice, Nude
  • Mice
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
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Baliko, F., Bright, T., Poon, R., Cohen, B., Egan, S. E., & Alman, B. A. (2007). Inhibition of notch signaling induces neural differentiation in Ewing sarcoma. Am J Pathol, 170(5), 1686–1694. https://doi.org/10.2353/ajpath.2007.060971
Baliko, Frank, Tamara Bright, Raymond Poon, Brenda Cohen, Sean E. Egan, and Benjamin A. Alman. “Inhibition of notch signaling induces neural differentiation in Ewing sarcoma.Am J Pathol 170, no. 5 (May 2007): 1686–94. https://doi.org/10.2353/ajpath.2007.060971.
Baliko F, Bright T, Poon R, Cohen B, Egan SE, Alman BA. Inhibition of notch signaling induces neural differentiation in Ewing sarcoma. Am J Pathol. 2007 May;170(5):1686–94.
Baliko, Frank, et al. “Inhibition of notch signaling induces neural differentiation in Ewing sarcoma.Am J Pathol, vol. 170, no. 5, May 2007, pp. 1686–94. Pubmed, doi:10.2353/ajpath.2007.060971.
Baliko F, Bright T, Poon R, Cohen B, Egan SE, Alman BA. Inhibition of notch signaling induces neural differentiation in Ewing sarcoma. Am J Pathol. 2007 May;170(5):1686–1694.
Journal cover image

Published In

Am J Pathol

DOI

ISSN

0002-9440

Publication Date

May 2007

Volume

170

Issue

5

Start / End Page

1686 / 1694

Location

United States

Related Subject Headings

  • Transfection
  • Signal Transduction
  • Sarcoma, Ewing
  • Reverse Transcriptase Polymerase Chain Reaction
  • Receptors, Notch
  • Pathology
  • Neurons
  • Mice, Nude
  • Mice
  • Humans