Loss of oestrogen receptor alpha in long-term antioestrogen-resistant cells: reversal by a c-src inhibitor

Excerpt

Tamoxifen still remains the most frequently used antioestrogen for the treatment of breast cancer. However, its efficacy is often limited by the emergence of acquired resistance and it has been suggested that, in some instances, this may involve oestrogen receptor (ER) loss. This study addresses this issue by examining long-term tamoxifen treatment of breast cancer cells and identifies that progressive ER loss does occur, leading to greatly increased aggressive tumour cell behaviour. Encouragingly, even after 30 months treatment, ER loss is reversible by a c-src inhibitor. Our data therefore provide a new model to study the cellular mechanisms associated with antihormone promoted ER loss and its possible prevention/reversal by signal transduction inhibitors. …