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-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.
van Agthoven
T
T
Department of Molecular Biology, Daniel den Hoed Cancer Center, University Hospital Rotterdam, Rotterdam, The Netherlands.
van Agthoven
T L
TL
Dekker
A
A
van der Spek
P J
PJ
Vreede
L
L
Dorssers
L C
LC
D000595:Amino Acid Sequence; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D001483:Base Sequence; D001665:Binding Sites; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics*; D002459:Cell Fusion; D003001:Cloning, Molecular; D018076:DNA, Complementary; D004273:DNA, Neoplasm; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression; D006801:Humans; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D012333:RNA, Messenger; D011953:Receptors, Cyclic AMP / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D013629:Tamoxifen / Q000494:pharmacology*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D018931:Antineoplastic Agents, Hormonal; C079747:CAR3 protein, Dictyostelium discoideum; D018076:DNA, Complementary; D004273:DNA, Neoplasm; D004965:Estrogen Antagonists; D012333:RNA, Messenger; D011953:Receptors, Cyclic AMP; D013629:Tamoxifen