Associations of ErbB2, β1-integrin and lipid rafts on Herceptin (Trastuzumab) resistant and sensitive tumor cell lines

Maria Magdalena Mocanu, Zsolt Fazekas, Miklós Petrás, Péter Nagy, Zsolt Sebestyén, Jorma Isola, József Tímár, John W. Park, György Vereb, János Szöllosi

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

ErbB2-mediated transmembrane signaling is a key target of novel anticancer agents such as Herceptin. Our comparison of Herceptin resistant (JIMT-1, MKN-7) and sensitive (SKBR-3, N-87) cell lines demonstrates the importance of ErbB2 association patterns involving integrins and lipid rafts. Flow cytometric FRET and confocal microscopic measurements revealed colocalization and molecular proximity between β1-integrins and ErbB2, as well as their association with lipid rafts. A weak functional interaction between ErbB2 and β1-integrin and the fact that ErbB2 did not co-patch with β1-integrins upon crosslinking imply that ErbB2 and β1-integrin define two distinct molecular association clusters from a functional point of view. Although Herceptin-sensitive cell lines expressed more ErbB2 and fewer β1-integrin molecules on their surface than their resistant counterparts, this finding probably does not explain the Herceptin resistant phenotype due to the weak interaction between β1-integrins and ErbB2. Our results imply that the true significance of the expression profile of proteins involved in oncogenesis can only be understood after characterizing their molecular interactions.

Original languageEnglish
Pages (from-to)201-212
Number of pages12
JournalCancer Letters
Volume227
Issue number2
DOIs
Publication statusPublished - Sep 28 2005

Keywords

  • Confocal microscopy
  • ErbB
  • Fluorescence resonance energy transfer
  • Herceptin resistance
  • Lipid rafts
  • Receptor tyrosine kinase
  • β1-integrin

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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