Notch and Schwann cell transformation

Yiwen Li, Prakash K. Rao, Rong Wen, Ying Song, David Muir, Peggy Wallace, Samantha J. Van Horne, Gihan I. Tennekoon, Tom Kadesch

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Benign plexiform neurofibromas in NF1 patients can transform spontaneously into malignant peripheral nerve sheath tumors (MPNSTs). Although mutations in the p53 gene have been found in a subset of MPNSTs and mouse models support a role for p53 mutations in malignant conversion, we found that each of three Schwann cell lines derived from human MPNSTs possessed active p53. One of the lines expressed the Notch intracellular domain (NICD), indicative of ongoing Notch signaling. Consistent with a role in malignancy, NICD was able to transform primary rat Schwann cells. Transformation was robust -NICD-transduced cells generated tumors in nude rats -and was associated with the loss of markers associated with Schwann cell differentiation. These data suggest that aberrant Notch signaling may contribute to the conversion of benign neurofibromas to MPNSTs.

Original languageEnglish
Pages (from-to)1146-1152
Number of pages7
JournalOncogene
Volume23
Issue number5
DOIs
StatePublished - Feb 5 2004
Externally publishedYes

Fingerprint

Schwann Cells
Neurilemmoma
Plexiform Neurofibroma
Nude Rats
Neurofibroma
Mutation
p53 Genes
Cell Differentiation
Neoplasms
Cell Line

Keywords

  • MPNST
  • Neurofibromatosis
  • NICD
  • Notch
  • p53
  • Schwann

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Li, Y., Rao, P. K., Wen, R., Song, Y., Muir, D., Wallace, P., ... Kadesch, T. (2004). Notch and Schwann cell transformation. Oncogene, 23(5), 1146-1152. https://doi.org/10.1038/sj.onc.1207068

Notch and Schwann cell transformation. / Li, Yiwen; Rao, Prakash K.; Wen, Rong; Song, Ying; Muir, David; Wallace, Peggy; Van Horne, Samantha J.; Tennekoon, Gihan I.; Kadesch, Tom.

In: Oncogene, Vol. 23, No. 5, 05.02.2004, p. 1146-1152.

Research output: Contribution to journalArticle

Li, Y, Rao, PK, Wen, R, Song, Y, Muir, D, Wallace, P, Van Horne, SJ, Tennekoon, GI & Kadesch, T 2004, 'Notch and Schwann cell transformation', Oncogene, vol. 23, no. 5, pp. 1146-1152. https://doi.org/10.1038/sj.onc.1207068
Li Y, Rao PK, Wen R, Song Y, Muir D, Wallace P et al. Notch and Schwann cell transformation. Oncogene. 2004 Feb 5;23(5):1146-1152. https://doi.org/10.1038/sj.onc.1207068
Li, Yiwen ; Rao, Prakash K. ; Wen, Rong ; Song, Ying ; Muir, David ; Wallace, Peggy ; Van Horne, Samantha J. ; Tennekoon, Gihan I. ; Kadesch, Tom. / Notch and Schwann cell transformation. In: Oncogene. 2004 ; Vol. 23, No. 5. pp. 1146-1152.
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