The Neurofibromatosis Type 2 Gene Product, Schwannomin, Suppresses Growth of NIH 3T3 Cells1

Cancer ¡sa multistep process that involves the activation of oncogenes and the inactivation of antioncogenes. Recently, a new putative tumor suppressor, the neurofibromatosis type 2 (NF2) gene, was mapped to chromosome 22, cloned, and found to encode for a new protein, merlin/ schwannomin, a member of the band 4.1 family of proteins. Members of this family have not been implicated previously in tumorigenesis. They possess significant homology in their MHz-terminal domain, which is thought to be important in the binding of the plasma membrane to the underlying actin cytoskeleton. To determine whether schwannomin may affect cell growth, we transfected NIH 3T3 cells with the wild type and an NF2 cDNA lacking 111 amino acids at the Ml, terminus. We observed slowing of growth and changes in cellular morphology only in cells ex pressing the wild-type NF2 cDNA. This finding suggests that schwan nomin can suppress growth directly and confirms its role in tumor sup pression. This system will provide a useful assay to identify important functional domains of the protein.