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

Jun Liu, Peiyee Lee, Ferruccio Galbiati, Richard N. Kitsis, Michael P. Lisanti

Research output: Contribution to journalArticle

92 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)C823-C835
JournalAmerican Journal of Physiology - Cell Physiology
Volume280
Issue number4 49-4
DOIs
StatePublished - 2001

Keywords

  • Caveolae
  • Caveolin
  • Signaling

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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