Antibodies to Estrogen Receptors

Introduction

Steroid receptors are ligand-dependent intracellular proteins that stimulate transcription of specific genes by binding to specific DNA sequences following activation by the appropriate hormone.

Estrogen steroid receptor (ESR) was first cloned in 1987 and has been shown to be expressed and transcriptionally active in a number of tissues including ovary, testis, prostate and brain. Besides the "classical" ESR (ER alpha or ESR1) a second estrogen binding receptor, referred to as ER beta or ESR2, has been cloned in rat and humans.

ER alpha is known to interact in a ligand dependent and independent manner with several known coactivators including Receptor-Interacting Protein 140 (RIP140/ERAP140), ERAP160, and Steroid Receptor Coactivator-1 (SRC-1) to enhance transcriptional activity of target genes. ER beta has been shown to be a high affinity estrogen binding protein capable of initiating transcription of genes under the control of estrogen response elements (ERE’s).

RNA distribution studies have shown ESR2 is transcribed in human thymus, spleen, ovary and testis as well as rat ovary and prostate. This distribution overlaps with but is not identical to the tissue distribution of ESR1 RNA. While ER beta RNA distribution has been studied, little is known about protein distribution under various hormone conditions. ER beta protein distribution may differ from RNA distribution and from ER alpha protein given the complex and differing activation, dimerization and translocation pathways exhibited by various steroid receptors under various ligand states.

Several isoforms of ER beta are known so far. The major differences between these splice variants were found in the C-terminal domain aa 459-530. These differ also in tissue expression. I.e. isoform beta 1 is expressed in testis and ovary, and at a lower level in heart, brain, placenta, liver, skeletal muscle, spleen, thymus, prostate, colon, bone marrow, mammary gland and uterus. Also found in uterine bone, breast, and ovarian tumor cell lines, but not in colon and liver tumors. Isoform beta 2 is expressed in spleen, thymus, testis and ovary and at a lower level in skeletal muscle, prostate, colon, small intestine, leukocytes, bone marrow, mammary gland and uterus. Isoform beta 3 is found in testis. Isoform beta 4 is expressed in testis, and at a lower level in spleen, thymus, ovary, mammary gland and uterus.

ERR (Estrogen-related receptor) family members (1, 2, and 3) share an almost identical DNA binding domain, which has 68% amino acid identity with that of estrogen receptor.

Estrogen-related receptor alpha (ESRRA, ERR1) acts as a site-specific transcription regulator and has been also shown to interact with estrogen and the transcripton factor TFIIB by direct protein-protein contact. The binding and regulatory activities of this protein have been demonstrated in the regulation of a variety of genes including lactoferrin, osteopontin, medium-chain acyl coenzyme A dehydrogenase (MCAD) and thyroid hormone receptor genes.

ESRRB (ERR2) encodes a protein with similarity to the estrogen receptor. Its function is unknown; however, a similar protein in mouse plays an essential role in placental development.

Estrogen-related receptor gamma (ESRRG, ERR3) has been suggested to affect differentiation of the brain, heart, and kidney. ERR gamma has been shown to be overexpressed in breast tumors, and its expression is correlated with levels of ErbB4, a likely indicator of preferred clinical course. As a result, ERR gamma has been suggested to be a potential biomarker for favourable clinical course and, possibly, hormonal sensitivity, and as a candidate target for therapeutic development.

Antibody Tools for the Detection of ER and ERR

Acris Antibodies offers a panel of antibodies to Estrogen receptor alpha and beta and Estrogen-related receptors suitable for immunological detection methods like immunohistochemistry, immunoprecipitation or Western blotting.

Fig.1: Staining of human breast carcinoma using SM1715 monoclonal antibody to ER alpha

Fig.2: Staining of human breast carcinoma using DRM001 rabbit monoclonal antibody to ER alpha

Fig.3: Staining of human ovary using SM1682 antibody to ER beta 1 isoform

Fig.4: Staining of primate amygdala using SP5198P antibody to ER beta

Fig.5: Staining of rat prostate tissue using SP5199P antibody to ER beta 1 isoform

Available antibody panel to Estrogen Receptor and Estrogen-related receptor

Estrogen receptor alpha antibody (anti- Estradiol-receptor / ER alpha / ESR1 / NR3A1), Estrogen receptor beta antibody (anti- ER beta / ESR2 / NR3A2), antibodies to Estrogen-related receptor alpha, beta and gamma: anti- ESRRA / ERR1 / NR3B1, anti- ESRRB / ERR2 / NR3B2 and anti- ESRRG / ERR3 / NR3B3

Literature:

Saunders, T.K. et al. (2000). Differential expression of estrogen receptor-alpha and -beta and androgen receptor in the ovaries of marmosets and humans. Biol. Reprod. 63: 1098-1105.

Torlakovic, E. et al. (2002). Prostate carcinoma expression of estrogen receptor-beta as detected by PPG5/10 antibody has postive association with primary Gleason grade and Gleason score. Pathology. 33: 646 - 651.

Saunders P. et al. (2002). ER beta 1 and the ER beta 2 splice variant (ER beta CX/ beta 2) are expressed in distinct cell populations in the adult human testes. J. Clin. Endocrinol. Metab. 87:2706-2715

Critchley T. et al. (2002). Wild Type Estrogen receptor (ER beta 1) and the splice variant (ER beta CX/ beta 2) are expressed within the human endometrium throughout the normal menstrual cycle. J. Clin. Endocrinol. Metab. 87:5265-5273.

Gaskell T. et al. (2003). Differential expression of two estrogen receptor beta isoforms in the human fetal testis during the second trimester of pregnancy. J. Clin. Endocrinol. Metab. 88:424-432. 7. Scobie G. et al. (2002). Human oestrogen receptors: differential expression of ER alpha and beta and the identification of ER beta variations. Steroids 67:985-995

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