Characterization and Consequences of Estrogen Receptor Exon Five Deletion.
Abstract
Estrogen, a key regulator of normal breast growth and differentiation, has been shown to promote both cancer cell proliferation and invasion (1,2). Although the estrogen receptor (ER alpha) is the major mediator of estrogen action, the precise mechanism by which ER alpha contributes to altered estrogen response in cancer remains unclear. Estrogen receptor (ER alpha) is one of many transcriptional regulatory proteins of the steroid receptor family that act principally as ligand-activated DNA-binding dimers (3). ER alpha has distinct functional domains, including two transcriptional activating regions (the NH-terminal AF1 and the COOH-terminal, ligand-dependent, AF2), an internal zinc finger, DNA-binding domain, dimerization regions, and several nuclear localization sequences (4) (Fig. 1 a). Like other ligand-activated transcriptional regulators (5), ER is not a single protein, but rather a set of proteins coded by two genes giving rise to ER, and ER (6) as well as isoforms generated by alternative splicing (exon skipping) of a single pre-mRNA. Since alternatively spliced ER,-rnRNAs were first noted in breast tumors and tumor cell lines, before their normal counterparts were thoroughly examined, it was proposed that overexpression of aberrant ER alpha isoforms is characteristic of breast cancer (7-23).
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 1996
- Accession Number
- ADA349470
Entities
People
- Beth Schachter
- Erina Erenburg
Organizations
- Icahn School of Medicine at Mount Sinai