Vorinostat Reexpressed Estrogen Receptor (Er) In Triple Negative Breast Cancer Cell Line Subtypes And Sensitized Cells To Tamoxifen And Indole-3-Carbinol In Vitro

Triple negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer. Although about 85% of breast cancers are estrogen positive, about 15% falls into this category. This subtype of cancer lacks targeted therapies receptors, such as the estrogen receptor (ER), progesterone receptor (PR), and the human epidermal growth factor receptor-2 (HER2). These patients are limited to cytotoxic chemotherapies with harsh side effects. In addition to occurring in younger women, other risk factors for TNBC include: being of African descent, BRCA1 mutation, a strong family history of breast cancer, lifestyle and environmental factors. Although mutations are involved in the initiation of TNBC, research has revealed that individuals are controlled by factors other than DNA sequences such as epigenetic mechanisms. Environmental and lifestyle related factors, such as the lack of population-based screening, and lack of access to care-factors, the urban environment, food deserts, social stress, racism, diet, lack of exercise, alcohol intake, and tobacco use (i.e. cigarette smoking) have all been described as factors associated with breast cancer related disparities. This study investigated the role of epigenetic mechanisms in the re-expression of ER receptors in triple negative breast cancer (TNBC) cells by examining the effects of a FDA-approved epigenetic drug (vorinostat) and the dietary agent (indole-3-carbinol) on three subtypes of triple negative breast cancer. Basal-like 2 (HCC1806), mesenchymal stem cell-like (MSL) MDA-MB-231 and mesenchymal (BT-549) cell lines were treated with vorinostat for 6, 12, 24 and 48 hrs alone. The ER was expressed in HCC1806 (3-fold) and MDA-MB-231 (5-fold) at 6 hr. The ER was not expressed in BT-549 cells at any time point. MTS assay demonstrated a significant decreased in proliferation (60%) in MDA-MB-231 when treated with vorinostat (10, 20 or 30 µM) and 10 µM of tamoxifen. Furthermore, a significant decrease (40%) in proliferation was also detected in MDA-MB-231 cells treatmented with I3C (200 µM) and vorinostat (10, 20 or 30 µM). Our preliminary results show that three triple-negative cell lines representing three subtypes responded different to treatment with vorinostat in re-expressing the estrogen receptor. However, these results showed promising result for the use of this drug in sensitizing triple negative breast cancer cells to tamoxifen and a dietary agent, indole-3-carbinol. Further functional studies are currently underway. Citation Format: Beverly D. Lyn-Cook, Julie Getz, Beverly Word, Rhonda Moore, Gustav Miranda-Carboni. Vorinostat reexpressed estrogen receptor (ER) in triple negative breast cancer cell line subtypes and sensitized cells to tamoxifen and indole-3-carbinol in vitro [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 18. doi:10.1158/1538-7445.AM2017-18