The antiestrogen tamoxifen is important in the treatment of hormone-dependent breast cancer, although development of resistance is inevitable. To unravel the molecular mechanisms of antiestrogen resistance, a search for involved genes was initiated. Retrovirus-mediated insertional mutagenesis was applied to human ZR-75-1 breast cancer cells. Infected cells were subjected to tamoxifen selection and a panel of resistant cell clones was established. Screening for a common integration site resulted in the identification of a novel gene designated BCAR3. Transfer of this locus by cell fusion or transfection of the BCAR3 cDNA to ZR75-1 and MCF-7 cells induces antiestrogen resistance. BCAR3 represents a putative SH2 domain-containing protein and is partly homologous to the cell division cycle protein CDC48.

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Keywords Amino Acid Sequence, Animals, Antineoplastic Agents, Hormonal/*pharmacology, Base Sequence, Binding Sites, Breast Neoplasms/drug therapy/*genetics, Cell Fusion, Cloning, Molecular, DNA, Complementary, DNA, Neoplasm, Drug Resistance, Neoplasm/genetics, Estrogen Antagonists/*pharmacology, Female, Gene Expression, Humans, Molecular Sequence Data, Protein Biosynthesis, RNA, Messenger, Receptors, Cyclic AMP/*genetics, Sequence Homology, Amino Acid, Tamoxifen/*pharmacology, Transcription, Genetic, Tumor Cells, Cultured
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Journal EMBO Journal
van Agthoven, T.L.A, Dekker, A, van der Spek, P.J, Vreede, L, Dorssers, L.C.J, & van Agthoven, A.J. (1998). Identification of BCAR3 by a random search for genes involved in antiestrogen resistance of human breast cancer cells. EMBO Journal, 17(10), 2799–2808. doi:10.1093/emboj/17.10.2799