Notch Signaling and Schwann Cell Transformation: Development of a Model System and Application to Human MPNSTs
Annual rept. 1 Mar 2006-28 Feb 2007
PENNSYLVANIA UNIV PHILADELPHIA
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This is an annual report that presents data obtained during the grants third 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 1 that the Notch targets Hes5 and c-Myc alone are unable to mimic the constitutive form of Notch, NICD, to effect transformation and 2 that NICD is NOT sufficient to transform primary Schwann cells. This latter observation is in stark disagreement with our earlier results. Accordingly, we have added a new Task that will address this discrepancy and elucidate the specific pathways that NICD alters in Schwann cells.
- Anatomy and Physiology
- Medicine and Medical Research