ErbB2, but not ErbB1, reinitiates proliferation and induces luminal repopulation in epithelial acini

Muthuswamy, S. K., Li, D. M., Lelievre, S., Bissell, M. J., Brugge, J. S. (September 2001) ErbB2, but not ErbB1, reinitiates proliferation and induces luminal repopulation in epithelial acini. Nature Cell Biology, 3 (9). pp. 785-792. ISSN 1465-7392

URL: http://www.ncbi.nlm.nih.gov/pubmed/11533657
DOI: 10.1038/ncb0901-785

Abstract

Both ErbB1 and ErbB2 are overexpressed or amplified in breast tumours. To examine the effects of activating ErbB receptors in a context that mimics polarized epithelial cells in vivo, we activated ErbB1 and ErbB2 homodimers in preformed, growth-arrested mammary acini cultured in three-dimensional basement membrane gels. Activation of ErbB2, but not that of ErbB1, led to a reinitiation of cell proliferation and altered the properties of mammary acinar structures. These altered structures share several properties with early-stage tumours, including a loss of proliferative suppression, an absence of lumen, retention of the basement membrane and a lack of invasive properties. ErbB2 activation also disrupted tight junctions and the cell polarity of polarized epithelia, whereas ErbB1 activation did not have any effect. Our results indicate that ErbB receptors differ in their ability to induce early stages of mammary carcinogenesis in vitro and this three-dimensional model system can reveal biological activities of oncogenes that cannot be examined in vitro in standard transformation assays.

Item Type: Paper
Uncontrolled Keywords: C-HA-RAS SIGNALING NETWORK GROWTH-FACTOR 3-DIMENSIONAL CULTURE RECEPTOR INTERACTIONS PROTEIN CAUSES CELL SURVIVAL EGF RECEPTOR MDCK CELLS IN-VITRO
Subjects: diseases & disorders > cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > ErbB
diseases & disorders > cancer > cancer types > breast cancer
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cell
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cell
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cell

bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types
CSHL Authors:
Communities: CSHL labs > Muthuswamy lab
Depositing User: Matt Covey
Date: September 2001
Date Deposited: 20 Dec 2013 17:38
Last Modified: 20 Dec 2013 17:38
PMCID: PMC2952547
Related URLs:
URI: http://repository.cshl.edu/id/eprint/29144

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