Abstract 1315: Regulation of Nodal expression by estrogen in hormone responsive human breast cancer cell lines.

Abstract Breast cancer is one of the most common cancers among Canadian women. Estrogen plays a key role in the in the normal growth and development of the breast and is also a major contributor to breast cancer growth. Recent studies have demonstrated that embryonic morphogen, Nodal is expressed in metastatic breast cancers and that its expression is correlated with breast cancer progression. In silico analysis of the Nodal promoter has revealed putative estrogen receptor binding sites (ERE) in proximity to the transcription start site. Our goal in this study is to investigate the role of estrogen on Nodal expression in human breast cancer cell-lines. Stimulation of MCF-7 and T47D breast cancer cell-lines that are estrogen receptor positive and express low levels of Nodal with 10nM of estradiol (E2) for varying amounts of time revealed that Nodal protein expression increases at about 48 hours after E2 exposure and persists up to 120 hours. Treatment with the E2 antagonist, ICI-182,780 (ICI) abrogates the E2-enhanced Nodal protein expression. Conversely, treating the MCF- 7 and T47D cells with recombinant Nodal resulted in a decreased expression of estrogen receptor in these cells both at the transcript and protein levels. These preliminary results suggest that there is a bidirectional interaction between estrogen receptor and Nodal in these cell-lines. Future experiments are aimed at understanding in depth this bidirectional phenomenon to provide better insight into hormonal regulation in metastatic breast cancer. Citation Format: Padmalaya Das, Daniela Quail, Lynne-Marie Postovit. Regulation of Nodal expression by estrogen in hormone responsive human breast cancer cell lines. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1315. doi:10.1158/1538-7445.AM2013-1315