Abstract 1295: Regulation of PAX2 activity by estradiol in breast cancer cells

Abstract

Abstract Most breast cancer deaths arise from tumour cells ability to produce distant metastases. Among breast tumour subtypes, luminal A tumours, which express the highest levels of estrogen receptor alpha, are associated with the poorest metastatic phenotype and with longest relapse-free survival. Usually active during embryogenesis, PAX2, a homeobox transcription factor, is of a particular interest in this context. It is preferentially activated in luminal A tumours in vivo and it was shown to downregulate the expression of ERBB2 (erythroblastic leukemia viral oncogene homolog 2, HER-2/neu), a well-documented proinvasive and pro-metastastic gene, in these cells in response to estradiol in vitro. However, the ability of estradiol to regulate PAX2 activity and ERBB2 expression in non-luminal breast cancer cells, and the intracellular mechanisms involved in estradiol-induced PAX2 activity in breast cancer cells, have not been investigated. Objective: The objective of our work was to compare the impact of estradiol exposure on PAX2 activation in luminal and non-luminal breast cancer cells, and to determine the molecular mechanisms mediating estradiol-induced activation in breast cancer cells. Hypothesis: Estradiol would induce PAX2 activity in breast cancer cells of the luminal subtype only, in an estradiol receptor alpha-dependent manner. Results: Basal PAX2 activity was higher in cell lines from luminal compared to non-luminal subtype. Activation of PAX2 by estradiol, as assessed by measuring PAX2 phosphorylation on serine 393 residue and ERBB2 expression, was selectively achieved in breast cancer cell lines of the luminal subtype. This process was blocked by estrogen receptor alpha antagonist ICI 182780. Conclusion: PAX2 activation by estradiol is selectively achieved in breast cancer cells of the luminal subtype, via ERα. We are currently investigating intracellular signaling pathways downstream of estrogen receptor alpha which could mediate estradiol-induced activation of PAX2 in luminal breast cancer cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1295. doi:1538-7445.AM2012-1295