We have previously demonstrated that, following acquisition of endocrine 
resistance, breast cancer cells display an altered growth rate together with 
increased aggressive behaviour in vitro. Since dysfunctional cell-cell adhesive 
interactions can promote an aggressive phenotype, we investigated the integrity 
of this protein complex in our breast cancer model of tamoxifen resistance. In 
culture, tamoxifen-resistant MCF7 (TamR) cells grew as loosely packed colonies 
with loss of cell-cell junctions and demonstrated altered morphology 
characteristic of cells undergoing epithelial-to-mesenchymal transition (EMT). 
Neutralising E-cadherin function promoted the invasion and inhibited the 
aggregation of endocrine-sensitive MCF7 cells, whilst having little effect on 
the behaviour of TamR cells. Additionally, TamR cells had increased levels of 
tyrosine-phosphorylated beta-catenin, whilst serine/threonine-phosphorylated 
beta-catenin was decreased. These cells also displayed loss of association 
between beta-catenin and E-cadherin, increased cytoplasmic and nuclear 
beta-catenin and elevated transcription of beta-catenin target genes known to be 
involved in tumour progression and EMT. Inhibition of EGFR kinase activity in 
TamR cells reduced beta-catenin tyrosine phosphorylation, increased 
beta-catenin-E-cadherin association and promoted cell-cell adhesion. In such 
treated cells, the association of beta-catenin with Lef-1 and the transcription 
of c-myc, cyclin-D1, CD44 and COX-2 were also reduced. These results suggest 
that homotypic adhesion in tamoxifen-resistant breast cancer cells is 
dysfunctional due to EGFR-driven modulation of the phosphorylation status of 
beta-catenin and may contribute to an enhanced aggressive phenotype and 
transition towards a mesenchymal phenotype in vitro.