Abstract
Apoptosis induction by staurosporine, ceramide, and Fas stimulation was investigated in the mouse thymoma cell line W7.2 and a panel of dexamethasone (dex)-resistant W7.2 mutant cell lines, Apt3.8, Apt4.8 and Apt5.8, and a Bcl-2 transfected W7.2 cell line (Wbcl2). While W7.2 cells were found to be sensitive to these apoptosis inducers, the Apt- mutants and Wbcl2 cells were shown to be resistant to some or all of the treatments. Specifically, all three Apt- mutants and Wbcl2 cells were found to be resistant to ceramide and Fas-mediated apoptosis, whereas, Apt4.8 and Apt5.8 were sensitive to staurosporine-induced apoptosis under conditions in which Apt3.8 and Wbcl2 cells were resistant. Measurements of caspase activity and cytochrome c release in cytosolic extracts of dex and staurosporine-treated cells indicated that the recessive Apt- mutations effect steps upstream of mitochondrial dysfunction. Steady-state RNA levels of apoptosis-associated gene transcripts showed that the observed differential resistance of the Apt- cell lines could not be explained by altered expression of numerous Bcl-2 or Fas related genes. Transient transfection of human Fas gene coding sequences into the Apt- mutants and Wbcl2 cells did not induce apoptosis, even though these same cell lines were sensitive to ectopic expression of the FADD and caspase 8 genes. Taken together, these data provide genetic evidence for the existence of shared components in the dex- and Fas-mediated apoptotic pathways in W7.2 cells.
Similar content being viewed by others
Article PDF
Author information
Authors and Affiliations
Corresponding author
Additional information
Edited by B.A. Osborne
Rights and permissions
About this article
Cite this article
Askew, D., Kuscuoglu, U., Brunner, T. et al. Characterization of Apt- cell lines exhibiting cross-resistance to glucocorticoid- and Fas-mediated apoptosis. Cell Death Differ 6, 796–804 (1999). https://doi.org/10.1038/sj.cdd.4400554
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.cdd.4400554
Keywords
This article is cited by
-
Identification of a novel cyclin required for the intrinsic apoptosis pathway in lymphoid cells
Cell Death & Differentiation (2009)
-
Regulation of differential pro- and anti-apoptotic signaling by glucocorticoids
Apoptosis (2007)
-
Recent insights into the mechanism of glucocorticosteroid-induced apoptosis
Cell Death & Differentiation (2002)
-
Thymocytes selected for resistance to hydrogen peroxide show altered antioxidant enzyme profiles and resistance to dexamethasone-induced apoptosis
Cell Death & Differentiation (2001)