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

Both ErbB1 and ErbB2 are overexpressed or amplified in breast tumours. To e xamine the effects of activating ErbB receptors in a context that mimics po larized epithelial cells in vivo, we activated ErbB1 and ErbB2 homodimers i n preformed, growth-arrested mammary acini cultured in three-dimensional ba sement membrane gels. Activation of ErbB2, but not that of ErbB1, led to a reinitiation of cell proliferation and altered the properties of mammary ac inar structures. These altered structures share several properties with ear ly-stage tumours, including a loss of proliferative suppression, an absence of lumen, retention of the basement membrane and a lack of invasive proper ties. 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 e xamined in vitro in standard transformation assays.