Apoptosis of mortal human fibroblasts transformed by the bovine papillomavirus E5 oncoprotein

Mortal human fibroblasts can be partially transformed by the bovine papillomavirus E5 oncoprotein through activation of the platelet-derived growth factor beta receptor. Here, we report that these cells undergo massive apoptosis 2 weeks after confluence. Although activation of caspase 3 was observed...

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Bibliographic Details
Published in:Molecular cancer research 2002-12, Vol.1 (2), p.122-136
Main Authors: YING ZHANG, LEHMAN, John M, PETTI, Lisa M
Format: Article
Language:English
Subjects:
Apoptosis
bcl-2-Associated X Protein
Biological and medical sciences
Caspase 3
Caspases - metabolism
Cell Division
Cell Line, Transformed
Cell Nucleus - metabolism
Cell physiology
Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes
Culture Media, Conditioned - pharmacology
Cytochrome c Group - metabolism
Cytosol - metabolism
Enzyme Activation
Fibroblasts - metabolism
Fibroblasts - pathology
Fundamental and applied biological sciences. Psychology
Humans
Immunoblotting
In Situ Nick-End Labeling
Microscopy, Fluorescence
Microscopy, Video
Molecular and cellular biology
Oncogene Proteins, Viral - metabolism
Protein Conformation
Proto-Oncogene Proteins - metabolism
Proto-Oncogene Proteins c-bcl-2 - metabolism
Subcellular Fractions - metabolism
Time Factors
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Summary:Mortal human fibroblasts can be partially transformed by the bovine papillomavirus E5 oncoprotein through activation of the platelet-derived growth factor beta receptor. Here, we report that these cells undergo massive apoptosis 2 weeks after confluence. Although activation of caspase 3 was observed in the apoptotic cells, it was not required for apoptosis. The appearance of the mitochondrial proteins cytochrome c and apoptosis-inducing factor in cytosolic and nuclear compartments, respectively, provided a basis for mitochondrial dysfunction and a caspase-independent mechanism of apoptosis in these cells. Although an activating conformational change in Bax also was evident in the apoptotic cells, enforced overexpression of Bcl-2 was insufficient to prevent apoptosis. Finally, a small peptide present in the conditioned medium from dying transformed cells appeared responsible for inducing apoptosis through affecting a conformational change in Bax and eventual relocalization of apoptosis-inducing factor to the nucleus. Thus, an atypical apoptotic pathway is activated in mortal human fibroblasts in response to transformation induced by sustained receptor tyrosine kinase activation.
ISSN:1541-7786
1557-3125