CD40 activation mediates p53-dependent cell cycle regulation in human multiple myeloma cell lines

It has been reported that the activation of multiple myeloma (MM) cells by CD40 induces proliferation, growth arrest, and apoptosis. To determine whet her the biologic sequelae of CD40 activation in MM cells depends on p53 fun ction, we identified temperature-sensitive p53 mutations in the RPMI 8226 ( tsp53E285K) and the HS Sultan (tsp53Y163H) MM cell lines. These cells were then used as a model system of inducible wtp53-like function because wild-t ype-like p53 is induced at permissive (30 degrees C) but not at restrictive (37 degrees C) temperatures. Using p21-luciferase reporter assays, we conf irmed that CD40 induces p53 transactivation in RPMI 8226 and HS Sultan cell s cultured under permissive, but not restrictive, conditions. Furthermore, CD40 activation of these MM cells under permissive, but not restrictive, te mperatures increased the expression of p53 and p21 mRNA and protein. Import antly, CD40 activation induced the proliferation of RPMI 8226 and HS Sultan cells at restrictive temperatures and growth arrest and increased subG1 ph ase cells at permissive temperatures. These data confirmed that CD40 activa tion might have distinct biologic sequelae in MM cells, depending on their p53 status. (C) 2000 by The American Society of Hematology.