Abstract
The role of Bcl-2 in TRAIL-induced apoptosis has been investigated in lymphoid cells. Here we show that the human prostatic carcinoma cell line PC3 was sensitive to TRAIL treatment whereas PC3 overexpressing of Bcl-2 was resistant. TRAIL receptors ligation in PC3 activated caspases -2, -3, -7, -8, and -9, induced Bid processing, dissipation of mitochondrial transmembrane potential (ΔΨm), and cytochrome c release. We have detected caspases -8 and -3 only in the cytosolic fraction of cells, but caspases -2, -7, and -9 were found both in cytosolic and mitochondrial fractions. Bcl-2 overexpression did not affect caspase-8 activation although it did change the processing pattern of caspase-3. At the same time, Bcl-2 overexpression inhibited the activation of mitochondrial localized caspases -2, -7, and -9. Bcl-2 also abrogated TRAIL-induced cytochrome c release and dissipation of ΔΨm. These findings suggest that TRAIL-induced apoptosis in the epithelial cell line PC3 depends both on mitochondrial integrity and caspase activation.
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Acknowledgements
The authors thank R Glover for technical assistance and A Gewies for assistance with Bcl-2 cDNA recloning. This research was supported by National Institutes of Health grant CA 76673.
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Rokhlin, O., Guseva, N., Tagiyev, A. et al. Bcl-2 oncoprotein protects the human prostatic carcinoma cell line PC3 from TRAIL-mediated apoptosis. Oncogene 20, 2836–2843 (2001). https://doi.org/10.1038/sj.onc.1204410
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DOI: https://doi.org/10.1038/sj.onc.1204410
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