Resistance of pleural mesothelioma cell lines to apoptosis:
relation to expression of bcl-2 and bax.
Narasimhan, Sudha Rani, Lin Yang, Brenda I. Gerwin, V. Courtney
Broaddus.
1 Department of Medicine and Lung Biology Center, San Francisco
General Hospital, San Francisco, California 94110. 2 Division of
Basic Sciences, National Cancer Institute, Bethesda, Maryland
20892
APStracts 5:0079L, 1998.
A failure of normal apoptosis, often due to mutant p53, may contribute
to the formation of a cancer and to its resistance to therapy.
Mesothelioma, an asbestos-induced tumor, is highly resistant to
therapy but generally expresses wild type p53. We asked whether
mesothelioma was resistant to apoptosis and whether resistance was
associated with altered expression of the anti-apoptotic protein Bcl
-2 or pro-apoptotic protein Bax. We found that 3 mesothelioma cell
lines (1 with wild type p53) were highly resistant to apoptosis
induced by oxidant stimuli (asbestos, H2O2) or non-oxidant stimuli
(calcium ionophore) compared to primary cultured mesothelial cells.
By immunostaining, 1 of these 3 lines expressed Bcl-2, but only
during mitosis. By immunoblotting, 3 of 14 additional mesothelioma
lines (9/14 with wild type p53) expressed Bcl-2 but all 14 of 14
expressed the pro-apoptotic Bax giving a low ratio of Bcl-2:Bax. We
conclude that mesothelioma cell lines are resistant to apoptosis and
that the failure in apoptosis is not explained by Bcl-2, but by other
mechanisms that counteract the proapoptotic effect of Bax.
Received 2 July 1997; accepted in final form 29 March 1998.
APS Manuscript Number L183-7.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 24 April 1998