Transcriptionally active non-ligand binding oestrogen receptors in breast cancer

Data were obtained on soluble oestrogen (ER) and progesterone (PR) receptors from 273 primary breast tumours, using an enzyme immunoassay (EIA) and ligand binding assay with dextran-coated charcoal (DCC) or isoelectric focussing separations. The p29 and total cathepsin D content was also assayed in the same samples. Tumours expressing ER (by either steroid binding assay or EIA) had higher levels of p29 than those which did not express the receptor (P < 0.0001). Moreover, tumours co-expressing ER, PR and p29 appeared to have higher levels of cathepsin D than those which were negative for at least one protein (P < 0.0001). Twenty out of the 273 human breast cancer samples, containing a level of ER positive by EIA, which did not bind labelled oestradiol, were identified; isoelectric focussing showed that such a receptor was also unable to bind hydroxytamoxifen. These tumours did not significantly differ from those in the whole population in their capacity to express ER (positive by EIA), PR, p29 and cathepsin D. It was concluded that the EIA can detect both a ligand binding ER and a receptor which is able to initiate PR transcription but does not bind radio-labelled ligands in vitro; such a receptor could have a bearing on the variability of tumour response to endocrine therapy.