Notch Signaling and Schwann Cell Transformation: Development of a Model System and Application to Human MPNSTs
Abstract
This is an annual report that presents data obtained during the grant's initial year of funding. The grant addresses the potential role of Notch signaling in the malignant transformation of neurofibromas to MPNSTs in patients with NF1. Our previous work has shown that constitutive expression of Notch can transform rat Schwann cells and that at least on MPNST-derived human Schwann cell line (of three examined) signals via Notch. This report includes novel results pertaining to two Tasks of the Statement of Work, including our observations that 1) Notch transformation of rat Schwann cells is accompanied by a loss of contact inhibition, 2) Notch signaling transiently down-regulates CyclinD1 expression in rat Schwann cells although full transformation is associated with abundant levels of CyclinD1, and 3) human MPNST cell lines down-regulate CyclinD1 in response to Notch, suggesting that these cells are not as fully transformed as NICDtransduced rat Schwann cells. The significance of these data is discussed in the context of additional Tasks described by the Statement of Work.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2005
- Accession Number
- ADA435693
Entities
People
- Tom R. Kadesch
Organizations
- University of Pennsylvania