Notch and BCR signaling synergistically promote the proliferation of Raji B-lymphoma cells

The evolutionarily conserved Notch signaling pathway plays a pivotal role in cell proliferation, apoptosis, and cell fate decision from invertebrates to vertebrates, and is oncogenic in some human hematopoietic malignancies. To Study the role of Notch signaling in B-lymphoma, we expressed a Soluble fragment of human Delta-like 1 (hDll 1) in E. coli, which was shown to activate the Notch signaling. Incubation of Burkitt's lymphoma Raji cells with the Soluble hDll 1 led to gamma-secretase-dependent up-regulation of a Notch downstream gene, Hes1. This treatment synergized with B-cell receptor (BCR)-mediated signaling to promote proliferation of Raji cells in vitro, which was cancelled by GSI. We further showed that Notch signaling significantly repressed, while gamma-secretase inhibitor (GSI) enhanced, natural apoptosis of Raji cells. Because c-myc is a downstream gene of both Notch signaling and BCR signaling, and GSI blocked c-myc expression in the presence of hDll1 and anti-IgM, Notch signaling might interact with BCR signaling at the level of c-myc expression to regulate proliferation and apoptosis of B-lymphoma cells. (C) 2008 Elsevier Ltd. All rights reserved.