Upregulation of caveolin-1 and caveolae organelles in Taxol-resistant A549 cells

Chia-Ping H. Yang, Ferruccio Galbiati, Daniela Volonté, Susan Band Horwitz, Michael P. Lisanti

Research output: Contribution to journalArticle

134 Citations (Scopus)

Abstract

Caveolin is a principal component of caveolae membranes. It has been demonstrated that the interaction of the caveolin scaffolding domain with signaling molecules can functionally inhibit the activity of these molecules. Taxol is an antitumor agent that suppresses microtubule dynamics and binds to microtubules thereby stabilizing them against depolymerization. The drug also has been implicated in the induction of apoptosis through activation of components in signal transduction cascades. Here we have investigated the role of caveolin in the development of drug resistance by examining the expression of caveolins in low- and high-level drug-resistant cell lines. Caveolin-1, but not caveolin-2, was upregulated in highly multidrug resistant SKVLB1 cells that express high levels of P-glycoprotein, and in low-level Taxol-resistant A549 cell lines that express low amounts of P-glycoprotein. Two drug-resistant A549 cell lines (one 9-fold resistant to Taxol and the other 1.5-fold resistant to epothilone B), both of which express no P-glycoprotein, demonstrate a significant increase in the expression of caveolin-1. These results indicate that in low-level epothilone B- or Taxol-resistant A549 cells, increased caveolin-1 expression occurs independently of P-glycoprotein expression. Electron microscopic studies clearly demonstrate the upregulation of caveolae organelles in Taxol-resistant A549 cells. Upregulation of caveolin-1 expression in drug-sensitive A549 cells was observed acutely beginning 48 h after incubation with 10 nM Taxol. Thus, caveolin-1 may play a role in the development of Taxol resistance in A549 cells. Copyright (C) 1998 Federation of European Biochemical Societies.

Original languageEnglish (US)
Pages (from-to)368-372
Number of pages5
JournalFEBS Letters
Volume439
Issue number3
DOIs
StatePublished - Nov 20 1998

Fingerprint

Caveolin 1
Caveolae
Paclitaxel
Organelles
Up-Regulation
Caveolins
P-Glycoprotein
Pharmaceutical Preparations
Cells
Microtubules
Caveolin 2
Signal transduction
Depolymerization
Molecules
A549 Cells
Drug Resistance
Antineoplastic Agents
Signal Transduction
Chemical activation
Electrons

Keywords

  • Caveolae
  • Caveolin
  • Drug resistance
  • P-glycoprotein
  • Taxol

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Upregulation of caveolin-1 and caveolae organelles in Taxol-resistant A549 cells. / Yang, Chia-Ping H.; Galbiati, Ferruccio; Volonté, Daniela; Band Horwitz, Susan; Lisanti, Michael P.

In: FEBS Letters, Vol. 439, No. 3, 20.11.1998, p. 368-372.

Research output: Contribution to journalArticle

Yang, Chia-Ping H. ; Galbiati, Ferruccio ; Volonté, Daniela ; Band Horwitz, Susan ; Lisanti, Michael P. / Upregulation of caveolin-1 and caveolae organelles in Taxol-resistant A549 cells. In: FEBS Letters. 1998 ; Vol. 439, No. 3. pp. 368-372.
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