Can Bcl-2-based Drug Resistance Be Reversed through Exposures to Multiple Environmental Stresses?
During differentiation of germinal center and mantle zone B cells, levels of Bcl-2 protein increase upon exposure to a variety of survival stimuli, and cells become more resistant to various stresses. This latter effect extends to B-cell lymphomas where increased expression of Bcl-2 plays a major role in oncogenesis and resistance to anticancer drug-induced apoptosis (Cory and Adams, 2002). Thus, Bcl-2 expression level plays a major role in lymphocyte survival, differentiation, lymphomagenesis, and in multi-drug cellular resistance. Of great interest is the question of whether, and under what circumstances, Bcl-2-based cellular resistance can be bypassed, resulting in extensive cell death in lymphocyte populations. The present study was directed toward addressing this question using the EW36 cell line as a model of human B-lineage lymphoid cells expressing high Bcl-2 protein and resistant to the induction of apoptosis by diverse chemical agents. We previously found that exposure of EW3
