Based on previous studies of the properties of
moxestrol, we hypothesized that a radiohalogenated analog of
moxestrol, [125I]11 beta-methoxy-17 alpha-iodovinyl-
estradiol [( 125I] MIVE2), should bind to the
estrogen receptor (ER) in some ovarian
adenocarcinomas (OVCA), thereby offering the potential for imaging and/or treatment of these
cancers. We used
monoclonal antibodies (H222, H226, and D547) against human
breast cancer ER to identify the [125I]MIVE2-binding moiety in OVCA cytosols that is found on high
salt sucrose gradients. After gel electrophoresis and western blotting, exposure of OVCA extracts to the ER
antibodies, followed by exposure to goat antirat serum and then rat
peroxidase antiperoxidase, demonstrated a moiety in OVCA that migrated indistinguishably from the ER in MCF-7 human
breast cancer cells and from that in specimens of
breast cancer tissue. Because few studies have demonstrated efficacy of
hormone management for OVCA, we also wanted to learn whether ER exists in multiple forms in OVCA, in view of the possibility that some forms may be inactive in regulating growth-dependent cell functions while retaining
estrogen-binding capacity. By incubating the
monoclonal antibodies H222, H226, and D547, each of which recognizes a different region on the ER
protein, with OVCA cytosol fractions, we demonstrated that ER in OVCA can exist in multiple forms, some of which fail to express an H226-recognized site and some of which fail to express a D547-recognized site. This observation indicates that a relationship may exist between the presence or absence of certain forms of ER in
ovarian epithelial cancer and a patient's response to
hormone therapy.