ANTIESTROGEN RESISTANCE IN ER POSITIVE BREAST-CANCER CELLS

Acquisition of the antiestrogen resistance by breast cancer cells in v ivo 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. Howeve r, clinical data suggest that, in about 30% of the cases, antiestrogen resistance arises even in the presence of estrogen receptors. Postula ted mechanisms leading to the latter phenotype include selection for v ariant receptor forms during treatment, development of novel metabolic pathways for the drug, loss of nuclear co-factors, or activation of s ignal transduction pathway that cross activate ER signals. We have use d an in vitro experimental system utilizing LY-2 cell line, an ER posi tive and antiestrogen resistant MCF-7 cell variant, to study the mecha nism of antiestrogen resistance in the presence of functional ER. Resu lt from a complementation experiment suggests that LY-2 phenotype is a recessive trait. Cloning of the genetic defect in the LY-2 cells woul d provide further insight for the mechanism of antiestrogen resistance in ER positive breast cancer cells.