The aim of this study was to investigate the interaction of
tamoxifen (TAM) with the so-called Type II
estrogen binding sites (
Type II EBS) in both the cytosolic and the nuclear fraction of the ER-negative A 2780 human
ovarian cancer cell line and in an ER-negative
ovarian cancer tissue. Although cytosolic and nuclear
Type II EBS in A 2780 cells showed substantially similar binding characteristics in terms of
ligand affinity and specificity, TAM, while exhibiting the ability to displace [3H]
estradiol from cytosolic
Type II EBS failed to interact with nuclear
Type II EBS. The ability of TAM to interact only with cytosolic
Type II EBS seems also to be a characteristic of
ovarian cancer tissue and to be shared by several TAM metabolites. The hypothesis that the interaction of TAM with cytosolic
Type II EBS could mobilize the true endogenous
ligand of
Type II EBS which would become available for binding to nuclear
Type II EBS was tested by incubating the nuclear fraction with the cytosolic fraction. In the presence of cytosol, TAM acquires the ability to displace the tracer from nuclear
Type II EBS but when the cytosolic fraction was DCC, stripped in order to remove the endogenous
ligand, the competing activity of TAM for nuclear
Type II EBS was abolished. Our results suggest that TAM does not interact with nuclear
Type II EBS, but can favor the nuclear binding of endogenous
ligand by displacing it from cytosolic
Type II EBS.