PTRF/cavin-1 is essential for multidrug resistance in cancer cells

J Proteome Res. 2013 Feb 1;12(2):605-14. doi: 10.1021/pr300651m. Epub 2013 Jan 4.

Abstract

Since detergent-resistant lipid rafts play important roles in multidrug resistance (MDR), their comprehensive proteomics could provide new insights to understand the underlying molecular mechanism of MDR in cancer cells. In the present work, lipid rafts were isolated from MCF-7 and adriamycin-resistant MCF-7/ADR cells and their proteomes were analyzed by label-free quantitative proteomics. Polymerase I and transcript release factor (PTRF)/cavin-1 was measured to be upregulated along with multidrug-resistant P-glycoprotein, caveolin-1, and serum deprivation protein response/cavin-2 in the lipid rafts of MCF-7/ADR cells. PTRF knockdown led to reduction in the amount of lipid rafts on the surface of MCF7/ADR cells as determined by cellular staining with lipid raft-specific dyes such as S-laurdan2 and FITC-conjugated cholera toxin B. PTRF knockdown also reduced MDR in MCF-7/ADR cells. These data indicate that PTRF is necessary for MDR in cancer cells via the fortification of lipid rafts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Antibiotics, Antineoplastic / pharmacology
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Caveolae / drug effects
  • Caveolae / metabolism
  • Caveolin 1 / genetics
  • Caveolin 1 / metabolism
  • Cell Line, Tumor
  • Doxorubicin / pharmacology
  • Drug Resistance, Multiple / drug effects
  • Drug Resistance, Multiple / genetics*
  • Drug Resistance, Neoplasm / drug effects
  • Drug Resistance, Neoplasm / genetics*
  • Female
  • Fluorescent Dyes
  • Gene Expression Regulation, Neoplastic*
  • Gene Knockdown Techniques
  • Humans
  • Membrane Microdomains / drug effects
  • Membrane Microdomains / genetics
  • Membrane Microdomains / metabolism
  • Phosphate-Binding Proteins
  • RNA, Small Interfering / genetics
  • RNA-Binding Proteins / antagonists & inhibitors
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antibiotics, Antineoplastic
  • CAV1 protein, human
  • CAVIN1 protein, human
  • CAVIN2 protein, human
  • Carrier Proteins
  • Caveolin 1
  • Fluorescent Dyes
  • Phosphate-Binding Proteins
  • RNA, Small Interfering
  • RNA-Binding Proteins
  • Doxorubicin