Steroid- and retinoid-mediated growth arrest and apoptosis in WEHI-231 cells: role of NF-kappa B, c-Myc and CKI p27(Kip1)

IgM cross-linking induces NF-kappa B inactivation, c-Myc down-regulation, a nd cyclin kinase inhibitor p27(Kip1) accumulation in WEHI-231 murine B lymp homa cells. p27(Kip1) up-regulation leads to a decreased cyclin-dependent k inase 2 activity, retinoblastoma protein hypophosphorylation, G1 arrest and apoptosis. Similar to membrane (m) IgM cross-linking in B lymphoma cells, steroids and retinoids down-regulate c-Myc (via NF-kappa B inactivation) an d induce apoptosis in T cell hybridomas and thymocytes. In this study, we d etermined if steroids and retinoids have similar effects in WEHI-231 cells. Our results show that steroids and retinoids induce NF-kappa B inactivatio n, c-Myc down-regulation, p27(Kip1) up-regulation, G1 arrest, and apoptosis . Importantly, these hormones enhance anti-IgM-induced apoptosis in WEHI-23 1 cells. Similar to mIgM signaling, all these effects are prevented by trea tment with CD40 ligand. Caspase inhibition, on the other hand, rescues cell s from steroid/retinoid-induced apoptosis, but has no effect on growth arre st, p27(Kip1) and c-Myc. Together, these findings suggest that steroids/ret inoids and mIgM cross-linking share a common signal transduction pathway le ading to G1 arrest and cell death.