Estrogen receptor antibodies: specificity and utility in detection, localization and analyses of estrogen receptor...

The role of estrogens in regulating cellular metabolism in many tissues is well documented. Estrogens regulate cellular activity by interacting with specific intracellular receptor proteins. Two estrogen receptor (ER) isoforms have been isolated, cloned and characterized. Estrogen receptor alpha (ERalpha) and beta (ERbeta) are ligand dependent transcriptional activators, which regulate gene expression via complex mechanisms requiring ligand binding, transformation, dimerization, and interaction with specific unique cis DNA hormone response elements (EREs) and co-activators and co-repressors. Studies of ER structure and function have been tremendously facilitated by the development of molecular and biologic probes. Cloning and functional studies of the ERalpha and ERbeta have delineated some of the structural requirements involved in receptor function. Immunochemical analyses together with biochemical and molecular approaches have contributed to our understanding of ER structure and function. Although antibodies to ER have been developed and utilized for the past two decades, there has yet to be a comprehensive review that discusses the utility and usefulness of these antibodies in receptor detection and analysis. In this review, we summarize a plethora of information concerning the development and characterization of site-directed monoclonal and polyclonal antibodies to the ERalpha and ERbeta. We provide critical discussion on the characteristics and utility of ER antibodies in analyses, characterization and localization of ER isoforms in various tissues. We also provide a comparison of the potential utility of the available antibodies in various immunochemical assays. An epitope map detailing the specific sites of antibody-receptor interactions is constructed based on the available information. The advent of antibodies with high specificity and titer had facilitated detection of ER isoforms in normal and neoplastic tissues. The advent of new antibodies remains a powerful tool for assessment of ER expression and post-translational modification and receptor function in many experimental systems.