Role of Nuclear Receptor Coregulators in Hormone Resistant Breast Cancer
Abstract
We propose that coregulatory proteins influence the direction of transcription by antagonist-occupied steroid receptors. We screened for such proteins and identified three cDNA fragments encoding peptides that interact with antagonist-bound PRs. The aims were to clone complete cDNAs; define the role of the unknown proteins on receptor activity; and determine the role of the unknown proteins in hormone dependency of breast cancers. Major findings: We have focused on one novel cDNA fragment, designated ORF#93. We cloned the full-length cDNA; localized the gene to chromosome l5q23.l; expressed the full-length protein; defined its tissue distribution; and determined that it is cytoplasmic. ORF#93 doesn't appear to have a ligand-specific effect on PR transcription, but it does have general transcriptional effects. Prom mammalian two-hybrid and GST pull-down assays, we've determined that ORF#93 interacts with hsp9O and that this is influenced by the presence of PR and its ligands. It's possible that ORF#93 functions to regulate key events in the formation of nascent PR, cytoplasmic chaperone interactions and translocation into the nucleus. If so, ORF#93 may play a key role in bringing PR to associate with cytoplasmic molecules with which PR would otherwise not interact.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2003
- Accession Number
- ADA425637
Entities
People
- Kathryn B. Horowitz
- Lisa Nitao
Organizations
- University of Colorado Health