ecdysterone and Lymphoma--B-Cell

Crosslinking of surface immunoglobulin (Ig) receptors with anti-IgM (anti-mu) but not anti-IgD (anti-delta) antibodies causes growth arrest and apoptosis in several extensively characterized B1-like lymphoma cell lines. While anti-mu stimulates a transient increase in c-myc mRNA and protein expression, followed by a rapid decline below the baseline level, anti-delta only causes a moderate increase in the expression of this oncogene, which returns to baseline levels within 24-48 hours. However, signals downstream from anti-delta can be converted into an apoptotic pathway by modulating PI3K activity, suggesting that PI3K is a critical rheostat controlling survival signals in B1 cell lines. Anti-mu-induced down-regulation of c-Myc is followed in time with an increase in the cyclin dependent kinase inhibitor, p27Kip1, in all anti-mu sensitive lymphoma lines. This increase correlates with growth arrest and apoptosis. The anti-mu-mediated decrease in c-Myc, increase in p27Kip1, growth arrest and apoptosis, can all be prevented via CD40/CD40L signaling. Inhibition of caspase activation, on the other hand, prevents anti-mu-induced apoptosis, but has no effect on c-Myc, p27Kip1, and G1 arrest. Interestingly, we also found that steroids and retinoids can mimic anti-mu-mediated signaling and lead to a loss of c-Myc, an increase in p27Kip1, G1 arrest, and apoptosis. Together, these data suggest that modulation of c-Myc and p27Kip1 protein levels is crucial for the life versus death decisions in murine immature B1-like lymphoma cells lines.

Topics: Antibodies, Anti-Idiotypic; Apoptosis; B-Lymphocyte Subsets; Caspases; CD40 Antigens; CD40 Ligand; Cell Cycle; Cell Cycle Proteins; Cell Survival; Cyclin-Dependent Kinase Inhibitor p27; Dexamethasone; Ecdysterone; Enzyme Activation; Enzyme Induction; Enzyme Precursors; G1 Phase; Gene Expression Regulation, Neoplastic; Genes, myc; Humans; Intracellular Signaling Peptides and Proteins; Lymphoma, B-Cell; Microtubule-Associated Proteins; Neoplasm Proteins; Neoplastic Stem Cells; Phosphatidylinositol 3-Kinases; Protein-Tyrosine Kinases; Proto-Oncogene Proteins c-myc; Receptors, Retinoic Acid; Recombinant Fusion Proteins; Retinoid X Receptors; RNA, Messenger; RNA, Neoplasm; Signal Transduction; Syk Kinase; Transcription Factors; Transfection; Tretinoin; Tumor Suppressor Proteins