Abstract
Abstract Over 200,000 cases of breast cancer are diagnosed within the United States, resulting in over 40,000 deaths annually. Of the many lifestyle habits that are associated with cancer development, various epidemiological observations have provided a strong link between increased alcohol consumption and breast cancer progression. Specifically, this observation was made in women on estrogen replacement therapy thus suggesting a possible synergistic link between alcohol and estrogen. Our laboratory has demonstrated that estrogen increases breast cancer neo-vascularization both in vivo and in vitro. Provided that alcohol and estrogen can potentially synergize to promote breast cancer progression, we hypothesize that this progression is attributed to an increase in tumor neo-vascularization. In the current study, Tg-1 murine mammary carcinoma cells were treated with varying concentrations of alcohol +/- estrogen and analyzed for angiogenesis markers, such as VEGF and eNOS, and the pro-proliferation marker, MEK. At 24 hours post treatment, VEGF and eNOS were upregulated in response to both estrogen and alcohol compared to untreated cells and cells treated with either alcohol or estrogen alone. MEK levels remained constant through the conditions with a marginal upregulation in presence of alcohol and estrogen when compared to untreated cells. To further characterize neo-vascularization, we performed a scratch wound assay using the murine endothelial cell line, SVEC4-10, which was cultured in Tg1-1 conditioned media. The scratch wound assay results indicated enhanced migration of endothelial cells in response to conditioned media from Tg1-1 cells cultured in the presence of both alcohol and estrogen. SVEC4-10, treated with Tg-1-1 conditioned media were processed by Western blot analyses for MEK expression. MEK was upregulated in SVEC4-10 cells cultured in the media obtained from cells cultured with both alcohol and estrogen, indicating enhanced proliferation. Our results indicate a pro-neovasculogenic effect elicited by alcohol and estrogen, as determined by enhanced proliferation and migration of endothelial as well as increased expression of the pro-vasculogenic markers, VEGF and eNOS. Future experiments will be aimed to characterize the expression of other essential pro-vasculogenic markers, such as basic fibroblast growth factor (bFGF) and angiopoietin (Ang). The identification of these cellular and metabolic markers will establish a biochemical link between estrogen activity and signal transduction induced cellular effects. Citation Format: Rachana R. Maniyar, Robert B. Bednarczyk, Ghada M. Ben Rahoma, Neha Tuli, Abraham Mittelman, Raj K. Tiwari, Robert Suriano. Provasculogenic effects of alcohol and estrogen: implications for breast cancer development. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3365.
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