An estrogen receptor positive MCF-7 clone that is resistant to antiestrogens and estradiol.
The antiestrogen tamoxifen has been successfully used to control estrogen receptor (ER) and progesterone receptor positive breast cancer. However, the development of antiestrogen resistance is frequently observed in patients following long term treatment. We have studied the development of antiestrogen resistance in vitro and established an antiestrogen resistant variant of MCF-7 cells (clone 5C) after long term culture in estrogen free medium. The growth of clone 5C cells was not altered by either estradiol-17 beta or the antiestrogens 4-hydroxytamoxifen and ICI 164,384. Estrogen-stimulated progesterone receptor and reporter gene expression were markedly reduced in 5C cells compared to wild type MCF-7 cells. Only minor alteration in the levels of ER and no alteration in the affinity of ER for ligand were found in 5C cells. No mutation of ER cDNA in 5C cells was detected by polymerase chain reaction and DNA sequencing. This study demonstrates that change(s) in ER-mediated gene expression rather than the amino acid sequence of the ER itself may be associated with the development of at least one form of antiestrogen resistance.
Jiang
S Y
SY
Department of Human Oncology, University of Wisconsin Comprehensive Cancer Center, Madison 53792.
Wolf
D M
DM
Yingling
J M
JM
Chang
C
C
Jordan
V C
VC
D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002999:Clone Cells / Q000187:drug effects / Q000378:metabolism; D004273:DNA, Neoplasm / Q000032:analysis; D004351:Drug Resistance; D066246:ErbB Receptors / Q000096:biosynthesis; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology*; D004967:Estrogens; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D009363:Neoplasm Proteins / Q000032:analysis*; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism / Q000473:pathology*; D016133:Polymerase Chain Reaction; D053284:Polyunsaturated Alkamides; D011374:Progesterone / Q000096:biosynthesis; D011960:Receptors, Estrogen / Q000032:analysis*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D015398:Signal Transduction; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology; D014162:Transfection; D016211:Transforming Growth Factor alpha / Q000096:biosynthesis; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism
D004273:DNA, Neoplasm; D004965:Estrogen Antagonists; D004967:Estrogens; D009363:Neoplasm Proteins; D053284:Polyunsaturated Alkamides; D011960:Receptors, Estrogen; D011993:Recombinant Fusion Proteins; D016211:Transforming Growth Factor alpha; D013629:Tamoxifen; C016601:afimoxifene; D011374:Progesterone; D004958:Estradiol; C051781:ICI 164384; D066246:ErbB Receptors