Antiestrogen resistance in ER positive breast cancer cells.
Acquisition of the antiestrogen resistance by breast cancer cells in vivo may result from a variety of mechanisms. The main pathway appears to involve loss of estrogen receptor (ER) expression or selection for ER negative cells among heterogenous population of tumor cells. However, clinical data suggest that, in about 30% of the cases, antiestrogen resistance arises even in the presence of estrogen receptors. Postulated mechanisms leading to the latter phenotype include selection for variant receptor forms during treatment, development of novel metabolic pathways for the drug, loss of nuclear co-factors, or activation of signal transduction pathway that cross activate ER signals. We have used an in vitro experimental system utilizing LY-2 cell line, an ER positive and antiestrogen resistant MCF-7 cell variant, to study the mechanism of antiestrogen resistance in the presence of functional ER. Result from a complementation experiment suggests that LY-2 phenotype is a recessive trait. Cloning of the genetic defect in the LY-2 cells would provide further insight for the mechanism of antiestrogen resistance in ER positive breast cancer cells.
Paik
S
S
Vincent T. Lombardi Cancer Center, Georgetown University, Washington, DC 20007.
Hartmann
D P
DP
Dickson
R B
RB
Lippman
M E
ME
D000230:Adenocarcinoma / Q000473:pathology*; D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D004351:Drug Resistance; D004965:Estrogen Antagonists / Q000494:pharmacology*; D004967:Estrogens; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D006822:Hybrid Cells / Q000187:drug effects; D008325:Mammary Neoplasms, Experimental / Q000473:pathology; D009363:Neoplasm Proteins / Q000032:analysis* / Q000502:physiology; D009376:Neoplasms, Hormone-Dependent / Q000473:pathology*; D011960:Receptors, Estrogen / Q000032:analysis* / Q000187:drug effects; D011980:Receptors, Progesterone / Q000032:analysis; D013629:Tamoxifen / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000502:physiology; D014407:Tumor Cells, Cultured
D004965:Estrogen Antagonists; D004967:Estrogens; D005938:Glucocorticoids; D009363:Neoplasm Proteins; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D016212:Transforming Growth Factor beta; D013629:Tamoxifen