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

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Annual rept. 1 Jul 1999-1 Jul 2000

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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 ERRalphas 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.

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  • Anatomy and Physiology
  • Medicine and Medical Research

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