The significance of the expression of ERR alpha as a potential biomarker in breast cancer

It was shown the functional crosstalk between ERR alpha and ER alpha in breast cancer, however, the biological significance of estrogen-related receptor alpha (ERR alpha) remains largely unclear. Therefore, we examined the expression of ERR alpha in 39 primary human breast cancer tissues and 19 matched normal tissues using RT-PCR and immunohistochemistry in the context of the aromatase, ER alpha and proliferation markers (c-myc, Ki-67) expression. Compared to the normal breast tissue, breast cancer tissues showed a slightly higher expression level of ERR alpha mRNA (mean 46.2 +/- S.D. 42.0, 57.7 +/- S.D. 58.7, respectively). However, ERR alpha mRNA levels in breast cancer tissues showed greater diversity than in normal tissues. Immunohistochemical analysis of breast cancers revealed perinuclear and cytoplasmic localization of ERR alpha. Our study shows that there is no correlation between ERR alpha and ER alpha expression. We demonstrated a positive correlation between ERR alpha and c-myc at the transcriptional level and statistically significant positive correlation between aromatase and the ERR alpha at protein level. It seems that ERR alpha could play an important role in the alternative pathway to classical estrogen receptors-dependent pathway in cell signaling. Development and use of ERRS modulators might lead in the future to design new well-tolerated and individualized therapeutic agents. (C) 2008 Elsevier Ltd. All rights reserved.