Bcl-2 plays a critical role in growth and in spontaneous or induced apoptosis in myeloma cell lines

Abstract

The role of bcl-2 in spontaneous and drug-induced apoptosis in multiple myeloma (MM) is not yet established, particularly since the frequency of t(14:18) in MM is relatively low. In recent studies, we have investigated the steady-state levels of bcl-2 mRNA transcripts and bcl-2 protein in 8 MM cell lines and found inverse correlation between the levels of bcl-2 and sensitivity to dexamethasone (DEX)-induced apoptosis. Moreover, we have shown that bcl-2 was further down-regulated in DEX sensitive cell lines, but not in DEX resistance cell lines, in the course of DEX-induced apoptosis (Int J Oncol 8: 719-726, 1996). Herein, we report the results of transfection studies of 2 DEX sensitive MM cell lines, expressing relatively low levels of bcl-2, with a bcl-2 inducible gene construct expressed under the control of lac repressor operon. Thus, switching-on of bcl-2 by IPTG resulted in increased bcl-2 protein in the cells, enhancement of cell growth, and a decrease in spontaneous apoptosis, concomitant with increased resistance to DEX. Switching-off of bcl-2 protein expression by removal of IPTG resulted in restoration of sensitivity to DEX-induced apoptosis. We, therefore, conclude that bcl-2 plays a central role in cell growth and in spontaneous and induced apoptosis in MM cell lines.