Abstract B46: Vorinostat modulates the expression of the progesterone receptor in subtypes of triple-negative breast cancer cell lines

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that is characterized by a lack of clinically significant levels of hormone receptors for estrogen (ER) and progesterone (PR) and the human epidermal growth factor receptor-2 (HER2). TNBC has a high cell proliferation rate and has been described as an “interval cancer,” developing between yearly mammograms. TNBC accounts for 10-15% of all breast cancers diagnosed, and risk factors include age (> 40) and mutational status of tumor-suppressor genes (p53, BRCA1). Additionally, Hispanic American, African American, and women of African descent have been shown to be 3x more likely to develop this more aggressive subtype. The lack of cell surface receptors for ER, PR, and Her2 makes these tumors unresponsive to conventional hormone or targeted therapy, and currently there are no FDA-approved targeted therapies for this disease. This, combined with a higher rate of relapse and shorter overall survival period, leads to an overall poor prognosis for this breast cancer subtype. Vorinostat is a histone deacetylase inhibitor and has been shown to exert effects through epigenetic mechanisms. Previous studies have shown its ability to re-express ERα in triple-negative breast cancer cells. In this study we examined whether Vorinostat can re-express the PR in subtypes of TNBC cell lines HCC70, HCC1143, HCC1806, and BT549 and render these resistant cells sensitive to cancer agents. Using real-time PCR and immunostaining, the re-expression of the PR receptor was shown in BT549 (4-fold), HCC70 (13-fold), HCC 1143 (5-fold), and HCC1806 (20-fold). PR is known to modulate ERα in breast cancer. Indole-3-carbinol (I3C) alone or in combination with tamoxifen decreased PR expression in HCC1806 and HCC70 cells. Tamoxifen and I3C also inhibited cell growth of triple-negative breast cancer cells with vorinostat. These results show promise for the use of vorinostat in sensitizing subtypes of triple-negative breast cancer cells to tamoxifen and a dietary agent, I3C. Furthermore, this study revealed that vorinostat can re-express critical receptors in triple-negative breast cancer, suggesting its possible use in combinational therapy for this aggressive form of breast cancer. Citation Format: Beverly Lyn-Cook, Fatemeh NouriEmamzadeh, Beverly Word, Rhonda Moore, Gustav Miranda-Carboni. Vorinostat modulates the expression of the progesterone receptor in subtypes of triple-negative breast cancer cell lines [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr B46.