Abstract
The potential role of caveolin-1 in apoptosis remains controversial. Here, we investigate whether caveolin-1 expression is proapoptotic or antiapoptotic using a well-defined antisense approach. We show that NIH/3T3 cells harboring antisense caveolin-1 are resistant to staurosporine-induced apoptosis, as assessed using cell morphology, DNA content, caspase 3 activation, and focal adhesion kinase cleavage. Importantly, sensitivity to apoptosis is recovered when caveolin-1 levels are restored. Conversely, recombinant stable expression of caveolin-1 in T24 bladder carcinoma cells sensitizes these cells to caspase 3 activation. Consistent with the observations using NIH/3T3 cells, downregulation of caveolin-1 in T24 cells substantially diminishes caspase 3-like activity. Loss of sensitivity to apoptotic stimulation is recovered by inhibition of the phosphatidylinositol 3-kinase pathway using LY-294002, suggesting a possible mechanism for the sensitizing effect of caveolin-1. Thus our results suggest that caveolin-1 may act as a coupling or sensitizing factor in signaling apoptotic cell death in both fibroblastic (NIH/3T3) and epithelial (T24) cells.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3T3 Cells
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Animals
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Apoptosis / drug effects
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Apoptosis / physiology*
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Caspase 3
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Caspases / metabolism
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Caveolin 1
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Caveolins / genetics*
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Chromones / pharmacology
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DNA, Antisense
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Down-Regulation / physiology
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Enzyme Activation / drug effects
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Enzyme Inhibitors / pharmacology
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Epithelial Cells / cytology*
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Epithelial Cells / enzymology
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Focal Adhesion Kinase 1
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Focal Adhesion Protein-Tyrosine Kinases
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Gene Expression / physiology
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Humans
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MAP Kinase Signaling System / drug effects
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MAP Kinase Signaling System / physiology*
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Mice
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases / metabolism
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Morpholines / pharmacology
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Phosphatidylinositol 3-Kinases / metabolism
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Protein-Tyrosine Kinases / metabolism
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Staurosporine / pharmacology
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Tumor Cells, Cultured / cytology
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Tumor Cells, Cultured / enzymology
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Urinary Bladder Neoplasms
Substances
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CAV1 protein, human
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Cav1 protein, mouse
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Caveolin 1
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Caveolins
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Chromones
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DNA, Antisense
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Enzyme Inhibitors
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Morpholines
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2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
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Phosphatidylinositol 3-Kinases
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Protein-Tyrosine Kinases
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Focal Adhesion Kinase 1
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Focal Adhesion Protein-Tyrosine Kinases
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PTK2 protein, human
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Ptk2 protein, mouse
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases
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CASP3 protein, human
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Casp3 protein, mouse
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Caspase 3
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Caspases
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Staurosporine