Role of Merlin in the Growth and Transformation of Arachnoidal Cells

摘要

This proposal is concerned with the functional role of merlin in arachnoidal and meningioma cells. In year 1, we developed meningioma-specific NF2 model systems. In Year 2, we characterized the phenotypic effects of these model systems. We showed that merlin loss enhances loss of contact inhibition of growth, increases anchorage independent growth and increases S-phase entry. In the final year, we have shown that merlin loss promotes tumor growth in athymic mice and have developed in vivo xenograft models of NF2 that can be monitored non-invasively using bioluminescent imaging using the in vitro matched cell lines. We have completed a microarray analysis of our matched NF2 cell lines, and have identified several potential downstream targets of merlin loss in meningiomas. Several of these are cell cycle and apoptosis-related proteins and members of other signaling pathways suggesting cross talk between merlin and these pathways.