BCL-2 EXPRESSION INHIBITS PROSTAGLANDIN E(2)-MEDIATED APOPTOSIS IN B-CELL LYMPHOMAS

Apoptosis is a critical mechanism in the maturation and maintenance of the immune system, However, the process by which cells die remains po orly understood. The proto-oncogene bcl-2 is considered important in d etermining whether cells enter an apoptotic pathway or survive. In thi s report, we first examined the differential sensitivity of immature ( CH31) and mature (CH12) B cell lymphomas to growth inhibition by PGE(2 ). The CH31 cell line was growth inhibited and underwent apoptosis in response to PGE(2), unlike its mature counterpart, CH12, Furthermore, endogenous levels of the anti-apoptotic protein Bcl-2 in CH31 cells we re low compared with CH12. To further investigate the role of Bcl-2 in PGE(2)- and cAMP-mediated cell death, a retroviral vector bearing the human bcl-2 gene was introduced into CH31. High expression of Bcl-2 i n CH31 had no effect on growth inhibition induced by PGE(2) or dibutyr yl cAMP. In contrast, increased expression of Bcl-2 completely inhibit ed PGE(2)- and cAMP-mediated DNA fragmentation and nuclear condensatio n, Finally, cell cycle analysis of Bcl-2-expressing CH31 cells demonst rated that PGE(2) increased the percentage of cells in G1, and analysi s of synchronized populations revealed that PGE(2) acts at all phases of the cell cycle to delay normal progression, These results support t he hypothesis that apoptosis induced through PGE(2) and cAMP signaling is sensitive to regulation by Bcl-2 in CH31 B cell lymphomas. Further more, unlike apoptosis, rgulation of PGE(2)- and cAMP-mediated growth inhibition in B lineage cells is a distinct and Bcl-2-independent mech anism.