Abstract 4402: Triple negative breast cancer progression is impacted by NR4A orphan nuclear receptor signaling

Abstract

Abstract PURPOSE: Despite the lack of an increased rate of breast cancer occurrence among African-American women, African-American women suffer greater mortality due to breast cancer as compared with other ethnic groups. A key factor in decreased survival among African American women may be the elevated occurrence of triple negative (ER-/PR-/HER2-) breast cancers. The negative response makes these patients ineligible for hormonal therapy or Her2 targeted therapies, often leaving cytotoxic chemotherapeutic strategies. The NR4A subfamily of orphan nuclear receptors have the potential to serve as distinct, specific pharmacological targets which can directly affect apoptosis and be exploited to design highly selective, less toxic regimens in triple negative breast cancer phenotypes. DESIGN METHOD: Using cell lines derived from MB468 cells, crystal violet staining and Alamar blue assays for cell viability, Western blot for protein expression, PCR for gene expression, and fluorescence microscopy for immunohistochemical staining and xenograft studies were performed. RESULTS: Breast tumor microarrays demonstrate that NR4A2 is highly expressed in the nucleus of normal, but not malignant breast epithelial cells. shRNA-mediated silencing of NR4A2 in triple negative breast cancer cells leads to increased proliferation. Studies also reveal shRNA-silencing of NR4A2 expression mediated partial resistance to doxorubicin, while overexpression leads to cell cycle arrest. Additionally, gene expression arrays show that overexpression of NR4A2 induces expression of angiogenic factors, and suppresses markers associated with epithelial-mesenchymal transition. CONCLUSION: These studies suggest that NR4A2 is a viable pharmacological target in triple negative breast cancer and may prove an effective means to address the disparity in survival rates of African-American women as compared to other ethnicities. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4402. doi:10.1158/1538-7445.AM2011-4402