Bcl-2 oncoprotein protects the human prostatic carcinoma cell line PC3 from TRAIL-mediated apoptosis.
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 (Delta Psi(m)), 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 Delta Psi(m). These findings suggest that TRAIL-induced apoptosis in the epithelial cell line PC3 depends both on mitochondrial integrity and caspase activation.
Rokhlin
O W
OW
Department of Pathology, The University of Iowa, Iowa, IA 52242, USA.
Guseva
N
N
Tagiyev
A
A
Knudson
C M
CM
Cohen
M B
MB
D048868:Adaptor Proteins, Signal Transducing; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism*; D003574:Cytochrome c Group / Q000378:metabolism; D004790:Enzyme Induction; D053200:Fas-Associated Death Domain Protein; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D008928:Mitochondria / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000503:physiopathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*; D053221:TNF-Related Apoptosis-Inducing Ligand; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D003574:Cytochrome c Group; C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein; D008562:Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D020169:Caspases