Role of a Novel Splice Variant of the Steroid Receptor Coactivator AIB1 in Breast Cancer
Abstract
In this proposal we have investigated the hypothesis that overexpression of a novel truncated version of AIB1 (Delta-3AIB1) that we have found to be overexpressed in breast cancer is import for tumor development by impacting upon nuclear hormone receptor function. We have examined the hypothesis that the novel AIB1 variant has an altered function that changes its interaction with nuclear receptors such as the estrogen or progesterone receptor. We propose that changes in the level of expression of the novel AIBi variant will support tumor progression and may well have prognostic significance for breast cancer. We have now determined that A3AIB1 is overexpressed relative to the full-length protein in breast cancer tumor samples and cell lines. We have determined that A3AIB1 is a significantly more active coactivator than full-length AIB1 on the estrogen and progesterone receptor (J. Biol. Chem. 276, 39736-3974l, 2001). We have shown that A3AIB1 overexpression increases estrogenic activity in agonists and SERMs such as tamoxifen (On co gene, in press 2003). In addition, a surprising finding is that overexpression of A3AIB1 can also potentiate BCE signaling. This implies that A3AIB1 can also drive non-hormone mediated proliferation in breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2003
- Accession Number
- ADA419708
Entities
People
- Anna T. Riegel
Organizations
- Georgetown University