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Am J Physiol Cell Physiol 280: C823-C835, 2001;
0363-6143/01 $5.00
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Vol. 280, Issue 4, C823-C835, April 2001

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

Jun Liu1, Peiyee Lee2, Ferruccio Galbiati1, Richard N. Kitsis2,3, and Michael P. Lisanti1,3

Departments of 1 Molecular Pharmacology and 2 Medicine and Cell Biology and 3 Albert Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, New York 10461

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.

caveolae; caveolin; signaling


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