Abstract 5141: Inhibition of HDAC1 leads to subtype switching in the SW13 adrenal adenocarcinoma line

Abstract

HDAC (histone deacetylase) enzymes are highly expressed in cancer cells and HDAC inhibitors have shown promise in clinical trials for certain patients in multiple types of cancer. In this context, the ability of the SW13 human adrenal adenocarcinoma line to switch between two well-established subtypes in response to HDAC inhibition is of interest. However, the previously characterized inhibitor (trichostatin A) is a toxic, broad-spectrum inhibitor affecting both class I and class II HDACs which have roles in the nucleus and cytosol, respectively. Multiple HDAC inhibitors are screened for their ability induce switching between the SW13 subtypes to identify which HDAC enzyme is necessary for controlling SW13 subtype switching. Results suggest that inhibition of class I HDAC1 increases the rate of conversion between SW13- to SW13+ cells. The effect of HDAC1 inhibition may be enhanced by HDAC3 inhibition as MS-275, an inhibitor specific for HDAC1 but with some specificity for HDAC3, is most effective, particularly when compared to the efficacy of depudecin, an HDAC1 specific inhibitor. After conversion to SW13+, there is increased acetylation on histone H3 but not histone H4 when compared to levels in SW13-, suggesting that the role of acetylation on the H3 tail plays an essential role in the subtype switch. SW13- cells do not express Brg1 or Brm, the mutually exclusive ATPase subunits of the SWI/SNF complex, and do not have an active SWI/SNF complex. Altered activity of this complex and the increased histone H3 acetylation may contribute to the extensive changes in gene expression observed between SW13+ and SW13- subtypes. Citation Format: Jessica M. Lam, Juliane Daggett, Kathryn J. Leyva, Elizabeth E. Hull. Inhibition of HDAC1 leads to subtype switching in the SW13 adrenal adenocarcinoma line. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5141. doi:10.1158/1538-7445.AM2014-5141