Notch and Schwann cell transformation

Oncogene. 2004 Feb 5;23(5):1146-52. doi: 10.1038/sj.onc.1207068.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic*
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Peripheral Nervous System Neoplasms / genetics
  • Peripheral Nervous System Neoplasms / metabolism
  • Protein Structure, Tertiary
  • Rats
  • Rats, Nude
  • Receptors, Notch
  • Schwann Cells / metabolism*
  • Signal Transduction
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Membrane Proteins
  • Receptors, Notch
  • Tumor Suppressor Protein p53