Breast cancer is widely and effectively treated with endocrine treatment. However, in many cases the tumours will eventually progress into an estrogen-independent and therapy-resistant phenotype. Retroviral insertion mutagenesis was used to generate this cell line in order to elucidate the molecular mechanisms underlaying endocrine therapy failure. Using this method the main genes conferring estrogen independence in human breast cancer cells where identified. Genes located in the immediate proximity of the retroviral integration site were characterised. Out of 15 candidate breast cancer antigen resistance (BCAR) genes, seven (AKT1, AKT2, BCAR1, BCAR3, EGFR2, GRB7 and TRERF1/BCAR2) were shown to directly underline estrogen…
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