IDENTIFICATION OF BCAR3 BY A RANDOM SEARCH FOR GENES INVOLVED IN ANTIESTROGEN RESISTANCE OF HUMAN BREAST-CANCER CELLS

The antiestrogen tamoxifen is important in the treatment of hormone-de pendent breast cancer, although development of resistance is inevitabl e. To unravel the molecular mechanisms of antiestrogen resistance, a s earch for involved genes was initiated. Retrovirus-mediated insertiona l mutagenesis was applied to human ZR-75-1 breast cancer cells. Infect ed cells were subjected to tamoxifen selection and a panel of resistan t cell clones was established. Screening for a common integration site resulted in the identification of a novel gene designated BCAR3. Tran sfer of this locus by cell fusion or transfection of the BCAR3 cDNA to ZR-75-1 and MCF-7 cells induces antiestrogen resistance. BCAR3 repres ents a putative SH2 domain-containing protein and is partly homologous to the cell division cycle protein CDC48.