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- Title
Bcl-2 oncoprotein protects the human prostatic carcinoma cell line PC3 from TRAIL-mediated apoptosis.
- Authors
Rokhlin, Oskar W; Guseva, Natalia; Tagiyev, Agshin; Knudson, C Michael; Cohen, Michael B
- 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. Oncogene (2001) 20, 2836–2843.
- Subjects
APOPTOSIS; CANCER cells; CELL lines; CYTOCHROME c; MITOCHONDRIA
- Publication
Oncogene, 2001, Vol 20, Issue 22, p2836
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1204410