%0 Journal Article
%T Estrogen receptor transcription and transactivation: Basic aspects of estrogen action
%A Stefan Nilsson
%A Jan-£¿ke Gustafsson
%J Breast Cancer Research
%D 2000
%I BioMed Central
%R 10.1186/bcr81
%X Jensen and Jacobsen were the first to describe that the biological effects of estrogen are mediated by a receptor protein [1]. The cloning of the ER, today renamed ER¦Á, was reported in 1986 [2,3]. For a long time, it was believed that only one ER existed; however, in 1995 a second ER, ER¦Â, was cloned from a rat prostate cDNA library by Gustafsson and colleagues [4**]. This finding has lead to a paradigm shift in our understanding of estrogen action, as will be evident from the different reviews in this issue of Breast Cancer Research.Since the discovery of ER¦Â in rat prostate, several groups have reported the cloning of ER¦Â from other species [5,6,7] or different sized ER¦Â isoforms, some with extended N-termini and others with truncations and/or insertions in the C-terminal ligand binding domain (LBD). The original ER¦Â clone encodes a protein of 485 amino acids, designated ER¦Â-485. ER¦Â-503 has an 18 amino acid residue in frame insertion into the LBD, and has a considerably lower affinity for E2 than ER¦Â-485. Both ER¦Â-503 and ER¦Â-485 bind to a consensus estrogen response element (ERE) and heterodimerize with each other and with ER¦Â [8,9]. The coactivator SRC-1 interacts with both ER¦Á and ER¦Â-485 in an estrogen-dependent manner but not with ER¦Â-503 [9]. An additional ER¦Â isoform, ER¦Âcx [10], is identical to ER¦Â-530 except that the last 61 C-terminal amino acids (exon 8) are replaced by 26 unique amino acid residues. The ER¦Âcx isoform shows no ligand binding activity and has no capacity to activate transcription of an estrogen-sensitive reporter gene [10]. Furthermore, ER¦Âcx shows preferential heterodimerization with ER¦Á rather than with ER¦Â, inhibiting ER¦Á DNA binding and having a dominant negative effect on ligand-dependent ER¦Â reporter gene transactivation [10].Various alternatively spliced forms of ER¦Á have also been reported [11,12,13,14,15,16]. Whether all isoforms or differentially spliced versions of ER¦Á and ER¦Â, respectively, are expressed as proteins or have
%K breast
%K central nervous system
%K estrogen receptor ¦Â
%K estrogen receptor knockout mice
%K heterodimerization
%K prostate
%K uterus
%U http://breast-cancer-research.com/content/2/5/360