Article abstract
Nature Cell Biology 3, 785 - 792 (2001)
Published online: 8 August 2001 | doi:10.1038/ncb0901-785
ErbB2, but not ErbB1, reinitiates proliferation and induces luminal repopulation in epithelial acini
Senthil K. Muthuswamy1,3, Dongmei Li1, Sophie Lelievre3,2, Mina J. Bissell2 & Joan S. Brugge1
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.
- Department of Cell Biology, 240, Longwood Ave, Harvard Medical School, Boston, Massachusetts 02115, USA
- Lawrence Berkeley National Laboratory, 1 Cyclotron Road, University of California, Berkeley, California, USA
- Present addresses: Cold Spring Harbor Laboratories, Cold Spring Harbor, New York 11724, USA (S.K.M.); Department of Basic Medical Sciences, Purdue University, West Lafayette, Indiana 47907, USA (S.L.)
Correspondence to: Joan S. Brugge1 e-mail: joan_brugge@hms.harvard.edu
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