BCL-2 PLAYS A CRITICAL ROLE IN GROWTH AND IN SPONTANEOUS OR INDUCED APOPTOSIS IN MYELOMA CELL-LINES - A STUDY WITH INDUCIBLE BCL-2 TRANSFECTION CONSTRUCTS

The role of bcl-2 in spontaneous and drug-induced apoptosis in multipl e myeloma (MM) is not yet established, particularly since the frequenc y of t(14:18) in MM is relatively low. In recent studies, we have inve stigated the steady-state levels of bcl-2 mRNA transcripts and bcl-2 p rotein in 8 MM cell lines and found inverse correlation between the le vels 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 co urse of DEX-induced apoptosis (Int J Oncol 8: 719-726, 1996). Herein, we report the results of transfection studies of 2 DEX sensitive MM ce ll lines, expressing relatively low levels of bcl-2, with a bcl-2 indu cible gene construct expressed under the control of lac repressor oper on. Thus, switching-on of bcl-2 by IPTG resulted in increased bcl-2 pr otein in the cells, enhancement of cell growth, and a decrease in spon taneous apoptosis, concomitant with increased resistance to DEX. Switc hing-off of bcl-2 protein expression by removal of IPTG resulted in re storation of sensitivity to DEX-induced apoptosis. We, therefore, conc lude that bcl-2 plays a central role in cell growth and in spontaneous and induced apoptosis in MM cell lines.