Estrogen receptors measurement

Particular attention is given to the development of new mechanistic biomarker assays and bioassays that can be used as indices of the toxicity of mixtures. These biomarker assays are typically based on toxic mechanisms such as brain acetylcholinesterase inhibition, vitamin K antagonism, thyroxin antagonism, Ah-receptor-mediated toxicity, and interaction with the estrogenic receptor. They can give integrative measures of the toxicity of mixtures of compounds where the components of the mixture share the same mode of action. They can also give evidence of potentiation as well as additive toxicity. 

Phytoestrogens can modulate expression of both sub-types of estrogen receptor (Patisaul et al, 1999,2001 Wang et al, 1996). However, the data is limited to measurements of mRNA content and it is unclear whether this differential expression results in any functional change. 

Brotherick, I., Lennard, T W J., Cook, S., Johnstone, R., Angus, B., Wmthereik, M P, and Shenton, B. K. (1995) Use of the biotinylated antibody Dako-Er ld5 to measure estrogen-receptor on cytokeratm positive cells obtained from primary breast cancer cells Cytometry 20, 74-80. 

Most steroid-sensitive cancers express specific cell surface receptors. Prednisone-sensitive lymphomas, estrogen-sensitive breast cancers, and prostatic cancers express specific receptors for corticosteroids, estrogens, and androgens, respectively. It is now possible to assay tumor specimens for steroid receptor content and to identify which individual patients are likely to benefit from hormonal therapy. Measurement of the estrogen receptor (ER) and progesterone receptor (PR) proteins in breast cancer tissue is now standard clinical practice. ER or PR positivity predicts response to hormonal therapy, whereas patients whose tumors are ER-negative generally fail to respond to such treatment. 

The estrogen receptor affinity of EM-652, the active drug of EM-800, was first measured in human breast cancer and normal human uterine cytosol (Asselin et al., 1980). As measured by competition studies in human breast cancer tissue, the affinity of EM-652 (Aj = 0.047 0.003 nM, RBA = 291, relative to 17p -estradiol set at 100), studied in the presence of... 

Stoessel S, Leclercq G (1986) Competitive binding assay for estrogen receptor in monolayer culture measure of receptor activity potency. J Steroid Biochem 25 677-682... 

Most hormone-sensitive cancers will express hormone receptors that can be assayed on biopsy specimens. This allows the clinician to predict whether an individual patient is likely to benefit from hormonal therapy. For example, it is now standard to measure estrogen receptor (ER) and progesterone receptor (PR) content in breast cancer tissue. Patients with ER- or PR-positive tumors are more likely to respond to antiestrogen therapy compared with patients who lack these hormone receptors. 

Cytoplasmic estrogen receptors are important prognostic indicators and are now routinely measured in samples of breast tissue after surgical removal of the tumor. Sixty percent of patients with carcinoma of the breast have tumors that are estrogen receptor positive. Approximately two thirds of patients with estrogen receptor-positive tumors respond to endocrine therapy 95% of the patients with estrogen receptor-negative tumors fail to respond. Therefore, the... 

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