Lymphoma models for B cell activation and tolerance. X. Anti-μ-mediated growth arrest and apoptosis of murine B cell lymphomas is prevented by the stabilization of myc

Abstract

Treatment of the WEHI-2131 or CH31 B cell lymphomas with anti-μ or transforming growth factor (TGF)-β leads to growth inhibition and subsequent cell death via apoptosis. Since anti-μ stimulates a transient increase in c- myc and c-fos transcription in these lymphomas, we examined the role of these proteins in growth regulation using antisense oligonucleotides. Herein, we demonstrate that antisense oligonucleotides for c-myc prevent both anti-μ- and TGF-β-mediated growth inhibition in the CH31 and WEHI-231 B cell lymphomas, whereas antisense c-fos has no effect. Furthermore, antisense c- myc promotes the appearance of phosphorylated retinoblastoma protein in the presence of anti-μ and prevents the progression to apoptosis as measured by propidium iodide staining. Northern and Western analyses show that c-myc message and the levels of multiple myc proteins were maintained in the presence of antisense c-myc, results indicating that myc species are critical for the continuation of proliferation and the prevention of apoptosis. These data implicate c-myc in the negative signaling pathway of both TGF-β and anti-μ.