Involvement of Human Estrogen Related Receptor Alpha 1 (hERR 1) in Breast Cancer and Hormonally Insensitive Disease
Abstract
A plausible candidate for a novel breast cancer prognosticator and target for therapy is the estrogen-related receptor a (ERRalpha), an orphan nuclear receptor that shares significant sequence identity with estrogen receptors (ERs) but does not bind estrogens. The goals of these studies are to asses ERRalpha 5 utility as a novel breast cancer prognosticator and to elucidate ERRalpha's role in modulating estrogen-responsive gene transcription. The data obtained to date indicate that: (i) ERRalpha is itself an estrogen-responsive gene (ii) ERRalpha express ion levels are significantly lower in a small panel of breast carcinomas relative to normal mammary tissues, (iii) the ERRalpha /ERalpha ratio significantly correlates with S-phase fraction and DNA ploidy within the tumors, (iv) ERRalpha represses estrogen-stimulated transcription in MCE-7 cells, (v) ERRalpha may modulate expression of numerous estrogen- responsive genes whose promoters contain identified ERRalpha -binding sites, and (vi) ERRalpha - dependent transcription can be activated through increased c-erbB2 signaling, a gene implicated in tamoxifen resistance. These findings may provide the basis for future studies to determine whether ERRalpha status may indicate sensitivity to hormonal therapies, progression to tamoxifen resistance, and disease outcome.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2000
- Accession Number
- ADB264652
Entities
People
- Eric A. Ariazi
- Janet Mertz
Organizations
- University of Wisconsin–Madison