Laminin activates the p185(HER2) oncoprotein and mediates growth inhibition of breast carcinoma cells

E. Tagliabue, E. Ardini, R. Pellegrini, M. Campiglio, R. Bufalino, M. Jeschke, B. Groner, M. I. Colnaghi, S. Ménard

Research output: Contribution to journalArticlepeer-review

Abstract

The interaction between laminin and the oncoprotein encoded by the c-erbB-2 oncogene was studied in vitro and in vivo in human breast carcinomas. In vitro analysis of breast carcinoma cell lines overexpressing p185(HER2) revealed that laminin, but not fibronectin, induced tyrosine phosphorylation and down-modulation of oncoprotein membrane expression. Laminin also specifically inhibited growth of p185(HER2)-positive cell lines. No direct binding between the recombinant extracellular domain of p185(HER2) and laminin was found. Induction of oncoprotein down-modulation by anti-integrin antibodies and coprecipitation of the oncoprotein with the β4 integrin subunit indicate that the interaction between p185(HER2) and laminin occurs through integrin molecules. The relevance of this in vitro observation was verified in vivo by analysing the prognostic value of p185(HER2) overexpression as a function of laminin production on archival paraffin-embedded sections of 887 primary breast tumours. The results revealed an association between p185(HER2) overexpression and unfavourable prognosis in tumours negative for laminin production, whereas in laminin-producing tumours, the oncoprotein overexpression was not associated with tumour aggressiveness.

Original languageEnglish
Pages (from-to)1427-1433
Number of pages7
JournalBritish Journal of Cancer
Volume74
Issue number9
Publication statusPublished - 1996

Keywords

  • Breast Cancer
  • Laminin
  • Oncoprotein

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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