Involvement of Human Estrogen Related Receptor Alpha 1 (hERR Alpha 1) in Breast Cancer and Hormonally Insensitive Disease
Annual summary rept. 1 Jul 2000- 1 Jul 2001
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The goal of these studies was to assess ERR alphas 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.
- Anatomy and Physiology
- Medicine and Medical Research