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Query: UMLS:C0338671 (Steroids)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
Steroids 2001 Jan
PMID:Estrogen receptor antibodies: specificity and utility in detection, localization and analyses of estrogen receptor alpha and beta. 1109 Jun 53

Estrogen receptor alpha (ERalpha) is phosphorylated on multiple amino acid residues. For example, in response to estradiol binding, human ERalpha is predominately phosphorylated on Ser-118 and to a lesser extent on Ser-104 and Ser-106. In response to activation of the mitogen-activated protein kinase pathway, phosphorylation occurs on Ser-118 and Ser-167. These serine residues are all located within the activation function 1 region of the N-terminal domain of ERalpha. In contrast, activation of protein kinase A increases the phosphorylation of Ser-236, which is located in the DNA-binding domain. The in vivo phosphorylation status of Tyr-537, located in the ligand-binding domain, remains controversial. In this review, I present evidence that these phosphorylations occur, and identify the kinases thought to be responsible. Additionally, the functional importance of ERalpha phosphorylation is discussed.
Steroids 2003 Jan
PMID:Estrogen receptor phosphorylation. 1247 18

Estrogen receptor alpha (ERalpha) is a member of a large conserved superfamily of steroid hormone nuclear receptors which regulates many physiological pathways by acting as a ligand-dependent transcription factor. Evidence is emerging that estrogens also induce rapid signaling to the downstream kinase cascades; however the mechanisms underlying this nongenomic function remain poorly understood. We have recently shown that ERalpha is methylated specifically by the arginine methyltransferase PRMT1 at arginine 260 in the DNA-binding domain of the receptor. This methylation event is required for mediating the extra-nuclear function of the receptor which would thereby interact with Src/FAK and p85 and propagate the signal to downstream transduction cascades that orchestrate cell proliferation and survival. Of particular interest, a possible role of methylated ERalpha in mammary tumorigenesis is also evident by the fact that, as demonstrated by immunohistochemical studies on a cohort of breast cancer patients, ERalpha is methylated in normal epithelial breast cells and is hypermethylated in a subset of breast cancers. Hypermethylation of ERalpha in breast cancer might cause hyperactivation of cellular kinase signaling, notably of Akt, described as a selective survival advantage for primary tumor cells even in the presence of anti-estrogens. A detailed understanding of the molecular mechanisms that control estrogen signaling in breast cancer is a crucial step in identifying new effective therapies.
Steroids
PMID:Methylation, a key step for nongenomic estrogen signaling in breast tumors. 2011 91