Estrogen Receptors
CHI Scientific Inc. is offering several lines of products and derivatives of estrogen receptor-α36 for research communities two category of products,1) estrogen receptos antibodies; and 2)estrogen recenptor-α36 cDNA constructs.

The diverse physiological functions of estrogens are mediated by specific structures designated as estrogen receptors (ERs). In 1986, the cloning of the estrogen receptor (ER) was first reported. Until 1996, it was assumed that there was only one ER responsible for all of the physiological and pharmacological effects of natural and synthetic estrogens and antiestrogens. However, in 1996, a second ER was cloned. Currently, the first ER discovered is referred to as ER-α, while the second is called ER-β. Figure 1. is an illustration of the existence of three ER-a isoforms.

Recently, ER-α was found actually exists as three sub-forms, ER-α66, 46 and 36 in terms of their size (Fig.1). All three isoforms of estrogen receptor α were identified and cloned. The shortest form of ER-α has a totally different binding capability for its ligands from the original estrogen receptor, which provides a basis for seeking SERMs specific for individual estrogen receptor subtypes, i.e. Receptor Specific SERM Discovery (RSSD). Importantly, different tissues at different time may express these receptor subtypes at different rations. It is critical to find SERM highly specific for a particular receptor type in order to develop drugs with high selectivity and reduce side effects.

The human ER-α36 (hER-α36) cDNA is an alternatively spliced variant of hER-α66. The predicted protein lacks both transcriptional activation domains of hER-α66 but retains its DNA binding domain, partial dimerization and ligand-binding domains, and 3 potential myristoylation sites located near to the N-terminus. These findings thus predict that hER-α36 functions very differently from hER-α66 in response to estrogen signaling. It was demonstrate that hER-α36 inhibits the estrogen-dependent and estrogen-independent transactivation activities of hER-α66 and hER-β. Furthermore hER-α36 is predominantly associated with the plasma membrane where it transduces both estrogen- and anti-estrogen-dependent activation of the MAPK/ERK signaling pathway and stimulates cell growth. It was concluded that hER-α36 is a predominantly membrane-based, unique alternatively spliced variant of hER-α66 that acts as a dominant-negative effector of both estrogen-dependent and estrogen-independent transactivation functions signaled through hER-α66 and ER-β. It also transduces membrane initiated estrogen-dependent activation of the MAPK/ERK mitogenic signaling pathway. The estrogen and anti-estrogen signaling pathways mediated by hER-α36 provide an alternative explanation for why some human breast cancers are resistant to and others are worsened by anti-estrogen therapy; the data suggest that hER-α36 also may be an important marker to direct therapy in human breast cancers and perhaps hER-α36 may also transduce estrogen-dependent signaling in other estrogen target tissues.

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