Contribution of p75NTR to Schwannoma Growth and Therapeutic Responses
Abstract
Neurofibromatosis type II (NF2) results from mutation in the tumor suppressor gene, NF2, leading to the development of multiple intracranial and spinal tumors including schwannomas. Our overall objective is to identify the fundamental differences between non-tumorous Schwann cells (SCs) and schwannoma cells and to determine the efficacy of therapies that target these differences in reducing schwannoma cell growth in culture and in animal models of human schwannoma disease. We find that the NF2 gene product, merlin, regulates p75NTR expression levels and signaling. This depends on the phosphorylation state of merlin. We also find that activation of p75NTR fails to induce apoptosis in SCs and schwannoma cells that lack functional merlin expression, in contrast to normal SCs. Further, activation of p75NTR in human VS cells protects the cells from some forms of cell death, including in response to c- Jun N-terminal kinase inhibitors. Finally, we find that human VS cells are highly resistant to ionizing radiation likely due to their low proliferative capacity.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2015
- Accession Number
- ADA620936
Entities
People
- Iram Ahmad
- J. J. Clark
- Jed Rasmussen
- Marlan R. Hansen
Organizations
- University of Iowa