Up-regulation of αvβ3 integrin expression is a novel molecular response to chemotherapy-induced cell damage in a heregulin-dependent manner

Luciano Vellon, Javier A. Menendez, Hong Liu, Ruth Lupu

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

αvβ3 integrin has a dual role in apoptosis. Whereas ligated αvβ3 activates cell survival pathways and suppresses pro-apoptotic signals, unligated αvβ3 or integrins bound to soluble ligands promote apoptosis. In this study, we assessed the role of α vβ3 in chemosensitivity of breast cancer cells expressing different levels of heregulin (HRG). Expression levels of the RGD-binding integrins αvβ3 were measured in MDA-MB-231 human breast cancer cells and its low HRG-expressing derivative (MDA-MB-231/AS31) treated with the microtubule-interfering agents (MIAs) paclitaxel and vincristine. Following treatment, only αvβ 3 levels were significantly increased in MDA-MB-231 cells. Interestingly, αvβ3 expression was more significantly up-regulated in the MDA-MB-231/AS31 cells than in the parental cells. This MIA-induced increase of αvβ3 expression was correlated with a decrease in cell viability and an increase in apoptosis in MDA-MB-231/AS31 cells, indicating that overexpression of αvβ3 is linked to chemotherapy-induced cell death in low HRG-expressing breast cancer models. Moreover, a paclitaxel-induced increase of αvβ3 was also observed in MCF-7 cells but not in an doxorubicin-resistant derivative that shows cross-resistance to paclitaxel, further providing evidence that the extent of αvβ3 up-regulation is related to cell damage. These results indicate that αvβ3 integrin is dramatically up-regulated in low HRG-expressing breast cancer models that are highly responsive to MIAs, thus providing a novel molecular marker of chemosensitivity influenced by HRG levels in breast cancer cells.

Original languageEnglish (US)
Pages (from-to)819-830
Number of pages12
JournalDifferentiation
Volume75
Issue number9
DOIs
StatePublished - Nov 2007

Keywords

  • Breast cancer
  • Chemosensitivity
  • Heregulin
  • Integrins
  • Paclitaxel
  • Vincristine
  • αβ

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology
  • Cancer Research

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