Laminin activates the p185HER2 oncoprotein and mediates growth inhibition of breast carcinoma cells.

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 p185HER2 revealed that laminin, but not fibronectin, induced tyrosine phosphorylation and down-modulation of oncoprotein membrane expression. Laminin also specifically inhibited growth of p185HER2-positive cell lines. No direct binding between the recombinant extracellular domain of p185HER2 and laminin was found. Induction of oncoprotein down-modulation by anti-integrin antibodies and coprecipitation of the oncoprotein with the beta 4 integrin subunit indicate that the interaction between p185HER2 and laminin occurs through integrin molecules. The relevance of this in vitro observation was verified in vivo by analysing the prognostic value of p185HER2 overexpression as a function of laminin production on archival paraffin-embedded sections of 887 primary breast tumours. The results revealed an association between p185HER2 overexpression and unfavourable prognosis in tumours negative for laminin production, whereas in laminin-producing tumours, the oncoprotein overexpression was not associated with tumour aggressiveness.

journal_name

Br J Cancer

authors

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

doi

10.1038/bjc.1996.560

subject

Has Abstract

pub_date

1996-11-01 00:00:00

pages

1427-33

issue

9

eissn

0007-0920

issn

1532-1827

journal_volume

74

pub_type

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