Caveolin-1 expression sensitizes fibroblastic and epithelial cells to apoptotic stimulation.

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.

• Authors: J Liu, P Lee, F Galbiati, R N Kitsis, M P Lisanti
• Journal: American journal of physiology. Cell physiology (Am J Physiol Cell Physiol) Vol. 280 Issue 4 Pg. C823-35 (Apr 2001) ISSN: 0363-6143 [Print] United States
• PMID: 11245599 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• CAV1 protein, human
• Cav1 protein, mouse
• Caveolin 1
• Caveolins
• Chromones
• DNA, Antisense
• Enzyme Inhibitors
• Morpholines
• 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
• Phosphatidylinositol 3-Kinases
• Protein-Tyrosine Kinases
• Focal Adhesion Kinase 1
• Focal Adhesion Protein-Tyrosine Kinases
• PTK2 protein, human
• Ptk2 protein, mouse
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3
• Mitogen-Activated Protein Kinases
• CASP3 protein, human
• Casp3 protein, mouse
• Caspase 3
• Caspases
• Staurosporine

Topics

• 3T3 Cells
• Animals
• Apoptosis (drug effects, physiology)
• Caspase 3
• Caspases (metabolism)
• Caveolin 1
• Caveolins (genetics)
• Chromones (pharmacology)
• DNA, Antisense
• Down-Regulation (physiology)
• Enzyme Activation (drug effects)
• Enzyme Inhibitors (pharmacology)
• Epithelial Cells (cytology, enzymology)
• Focal Adhesion Kinase 1
• Focal Adhesion Protein-Tyrosine Kinases
• Gene Expression (physiology)
• Humans
• MAP Kinase Signaling System (drug effects, physiology)
• Mice
• Mitogen-Activated Protein Kinase 1 (metabolism)
• Mitogen-Activated Protein Kinase 3
• Mitogen-Activated Protein Kinases (metabolism)
• Morpholines (pharmacology)
• Phosphatidylinositol 3-Kinases (metabolism)
• Protein-Tyrosine Kinases (metabolism)
• Staurosporine (pharmacology)
• Tumor Cells, Cultured (cytology, enzymology)
• Urinary Bladder Neoplasms