Accession Number : ADB281790


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


Descriptive Note : Annual summary rept. 1 Jul 2000- 1 Jul 2001


Corporate Author : WISCONSIN UNIV-MADISON


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


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/b281790.pdf


Report Date : Aug 2001


Pagination or Media Count : 29


Abstract : The goal of these studies was to assess ERR alpha's utility as a novel breast cancer biomarker. Using real-time quantitative polymerase chain reaction assays, we profiled mRNA levels in random clinical breast cancers (n = 38) and normal mammary epithelial cells (MECs) enriched from reduction mammoplasties (n = 9). These studies showed that: (i) ERR alpha was overexpressed in approximately 10 % of tumors; (ii) ERR alpha mRNA levels were significantly higher in progesterone receptor (PgR) -negative tumors (those lacking functional ER alpha) than in PgR-positive tumors; (iii) ERR alpha mRNA was more abundant than ER alpha, ER beta, ERR beta, and ERR gamma in PgR-neg tumors; (iv) ERR alpha expression correlated with ErbB2, ErbB3 and ER% expression by Spearman analysis; and (v) ERR alpha expression patterns were ordered together with ErbB2, ErbB3, and EGFR by cluster analysis. Therefore, ERR alpha may be a target of ErbB signaling. ErbB members signal via the mitogen-activated protein kinase pathway and ErbB2 has been associated with tamoxifen resistance. Hence, the following hypothesis was developed: ERR alpha, independent of ER alpha, potentiates transcription of genes whose promoters contain estrogen- response elements in tumors containing high MAPK activity due to overexpression of ErbB members. Thus, ERR alpha status may indicate sensitivity to hormonal and ErbB2-based therapies.


Descriptors :   *HORMONES , *RECEPTOR SITES(PHYSIOLOGY) , *ESTROGENS , *BREAST CANCER , EPITHELIUM , ENZYMES , DISEASES , NEOPLASMS , GENES , RESPONSE(BIOLOGY) , CELLS(BIOLOGY) , RIBONUCLEIC ACIDS , MAMMARY GLANDS


Subject Categories : Anatomy and Physiology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE