26/01/12 - A powerful breast cancer research antibody

ER-α36 Antibody

Estrogens control a variety of physiological and disease-linked processes that include reproduction, bone remodeling, and breast cancer. Estrogenic effects are transduced via genomic and non-genomic signaling through steroid hormone nuclear Estrogen Receptors (ERs), ER-α66 and ER-α36, respectively. Nuclear-localized ER act directly on genes at Estrogen Responsive Elements (ERE) as ligand-induced transcription factors, while extranuclear estrogen signaling occurs via protein kinase activation.¹

Estrogen receptors ER-α66 and ER-α36 share overlapping gene sequences, but have distinct functions.² Full length ER-α66 is a ligand-induced transcription factor that acts at ERE, and is characteristically detected in the nucleus of breast cancer specimens by immunohistochemistry. ER-α66 has been shown to suppress gene expression of ER-α36.³

The ER-α36 transcript initiates from a promoter in the first intron of the ER-α66 gene, and while it retains the DNA-binding domain and partial dimerization and ligand-binding domains, it lacks both transcriptional activation domains of ER-α66, and replaces the last 138 amino acids with a unique C-terminal 27-amino acid domain.² In contrast to ER-α66, ER-α36 localizes primarily at the plasma membrane and cytoplasm.² It responds to both estrogens and antiestrogens by transducing membrane-initiated signaling cascades, stimulating proliferation, and possibly contributing to a more aggressive phenotype in breast carcinomas.⁴ ER-α36 may act dominant-negatively on transactivation functions signaled through ER-α66 and ER-β.⁵ In ER-α36-overexpressing cancer cells, tamoxifen treatment fails to block the ER-α36-mediated activation of the MAPK/ERK pathway, and stimulates cell growth.⁵

ER-α36 physically interacts with the EGFR/Src/Shc complex and mediates estrogen-induced phosphorylation of epidermal growth factor receptor (EGFR) and Src.⁶ ER-α36 mediates non-genomic estrogen signaling through the EGFR/Src/ERK signaling pathway in ER-negative breast cancer cells, which suggests that a subset of ER-negative breast tumors that express ER-α36 retain responsiveness to mitogenic estrogen signaling.⁶ Thus, ER-α36 expression and function could be an essential diagnostic and prognostic factor of breast cancer.⁷

Cell Applications, Inc., have developed a unique ER-α36 Antibody (Cat# CY1109) that specifically detects endogenous ER-α36 by Western blotting, and ER-α36 in paraffin-embedded human breast cancer tissue by immunohistochemical analysis. This antibody is a powerful tool for both basic and clinical studies on ER-α36.

Additionally, we provide a panel of antibodies specific to other estrogen receptor isoforms, including ER-α66 and phospho-ER-α66, ER-β and phospho-ER-β, as well as antibodies to other steroid hormone receptors.

References:
1. Wang, Q. et al: J. Biol. Chem. 286:14737-43, 2011.
2. Wang, Z. et al: Biochem. Biophys. Res. Commun. 336(4):1023-7, 2005.
3. Zou, Y. et al: FEBS Lett. 583:1368-74, 2009.
4. Lee, L.M.J. et al: Anticancer Res. 28(1B): 479-483, 2008.
5. Wang, Z.Y. et al: Proc Natl Acad Sci U S A. 103(24): 9063-8, 2006.
6. Zhang, X.T. et al: Oncogene 30:770-80, 2011.
7. Semir, V. et al: J. Clin. Path. 64:54-7, 2011.