Abstract 4653: Genomics of regulatory crosstalk between PPAR gamma & 14-3-3 genes in breast cancer cells

Abstract

PPARγ, a ligand-stimulated transcription factor with differentiation promoting activity is overexpressed in a variety of cancers. Perturbation of PPAR-γ signaling is now believed to be a strategy for treatment of several cancers, including breast cancer. A set of genes regulated by PPAR-γ ligands is expected to mediate the antiproliferative and prodifferentiation effects in cancer cells. Because 14-3-3 family of proteins shows a debatable activity and varying expression levels in different tumors, in the studies presented here we explored the transcriptional regulatory role of Pioglitazone on the seven 14-3-3 isoforms presenting in MCF-7 breast cancer cells. This study demonstrated that the potent PPAR-γ agonist, Pioglitazone exerted a regulatory role on expression of 14-3-3 genes where it upregulated 14-3-3 gamma, epsilon, zeta and tau by 3.8, 5.2, 2.7 and 739 folds, respectively. However, it had a negative regulatory effect on 14-3-3 beta, sigma and Eta by 16.94, 4.58 and 2.12 folds, respectively compared with control cells. These results correlated with growth arrest and a great increase in BRCA1 gene expression by 1076 folds. In summary, these findings are the first time showing that PPAR-γ regulates 14-3-3 genes and raises question whether PPAR-γ ligands mediate their anticancer effects via regulation of 14-3-3 proteins. Selected References: 1. Bridges, D. and G.B. Moorhead. 2005. 14-3-3 proteins: a number of functions for a numbered protein. Sci. STKE 2005(296):re10. 2. Chearwae, W. and J. Bright. 2008. PPARγ agonists inhibit growth and expansion of CD133+; brain tumour stem cells. Brit. J. Cancer 99(12): 2044-2053 Citation Format: Ashraf A. Khalil, Nihal F. Kabapy, Fouad N. Sharabi. Genomics of regulatory crosstalk between PPAR gamma & 14-3-3 genes in breast cancer cells [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 4653. doi:10.1158/1538-7445.AM2017-4653