Accession Number : ADB264652


Title :   Involvement of Human Estrogen Related Receptor Alpha 1 (hERR 1) in Breast Cancer and Hormonally Insensitive Disease


Descriptive Note : Annual rept. 1 Jul 1999-1 Jul 2000


Corporate Author : WISCONSIN UNIV-MADISON


Personal Author(s) : Ariazi, Eric A ; Mertz, Janet


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/b264652.pdf


Report Date : Aug 2000


Pagination or Media Count : 42


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.


Descriptors :   *HORMONES , *GENES , *RESPONSE(BIOLOGY) , *RECEPTOR SITES(PHYSIOLOGY) , *ESTROGENS , *BREAST CANCER , IONS , RATIOS , TISSUES(BIOLOGY) , HUMANS , PANELS , DISEASES , SENSITIVITY , DEOXYRIBONUCLEIC ACIDS , THERAPY , BINDERS , MODULATION , MAMMARY GLANDS , NORMALITY


Subject Categories : Anatomy and Physiology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE