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Notch Signaling and Schwann Cell Transformation: Development of a Model System and Application to Human MPNSTs
Annual rept. 1 Mar 2005-28 Feb 2006
PENNSYLVANIA UNIV PHILADELPHIA
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This is an annual report that presents data obtained during the grant s second 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 one Task of the Statement of Work, including our observations that 1 Notch transformation of rat Schwann cells is accompanied alterations in the cell cycle profile, consistent with an up-regulation in CyclinD1 expression, 2 CyclinD1 expression is upregulated, in part, at the level of transcription, 3 Notch-mediated transformation requires signaling through PI3 Kinase and PKA, but not Jak-Stat, and 4 the process of Notch-mediated transformation is qualitatively distinct from that initiated by Notch ligands. The significance of these data is discussed in the context of additional Tasks described by the Statement of Work.
APPROVED FOR PUBLIC RELEASE