RESISTANCE OF PLEURAL MESOTHELIOMA CELL-LINES TO APOPTOSIS - RELATIONTO EXPRESSION OF BCL-2 AND BAX

A failure of normal apoptosis, often due to mutant p53, may contribute to the formation of a cancer and to its resistance to therapy. Mesoth elioma, an asbestos-induced tumor, is highly resistant to therapy but generally expresses wild-type p53. We asked whether mesothelioma was r esistant to apoptosis and whether resistance was associated with alter ed expression of the antiapoptotic protein Bcl-2 or proapoptotic prote in Bar. We found that three mesothelioma cell lines (1 with wild-type p53) were highly resistant to apoptosis induced by oxidant stimuli (as bestos, H2O2) or nonoxidant stimuli (calcium ionophore) compared with primary cultured mesothelial cells. By immunostaining, one of these th ree lines expressed Bcl-2 but only during mitosis. By immunoblotting, 3 of 14 additional mesothelioma lines (9 of 14 with wild type p53) exp ressed Bcl-2 but all 14 of 14 expressed the proapoptotic Bar, giving a low ratio of Bcl-2 to Bar. We conclude that mesothelioma cell lines a re resistant to apoptosis and that the failure in apoptosis is not exp lained by Bcl-2 but by other mechanisms that counteract the proapoptot ic effect of Bax.