Failure to disengage PI-3K pathway signaling confers Anti-IgM resistance to growth arrest and apoptosis in the CH12 B-cell lymphoma

摘要

We and others have firmly established that surface IgM receptor (sIgM-R) crosslinking with antibodies to the i heavy chain (anti-i) leads to growth arrest and apoptosis in a series of well characterized B-cell lymphomas. This requires ablation of c-Myc protein expression and the concomitant induction of the cyclin-dependent-kinase inhibitor, p27Kip1. The signaling mechanisms regulating c-Myc and p27Kip1 protein expression are poorly understood. However, we recently established that sIgM-R mediated down-modulation of the PI-3K pathway directly affected c-Myc and p27Kip1 expression and accurately predicted growth