Abstract 1675: MEF2 plays a significant role in the tumor inhibitory effects of agarose encapsulated RENCA cells through the EGF receptor

Identification of the molecular targets involved in the tumor growth inhibition induced by agarose encapsulated mouse renal adenocarcinoma (RENCA) cells will aid in an understanding of the mechanism of action and may allow for the discovery of key targets for therapeutic intervention. The epidermal growth factor receptor (EGFR/ERBB1/HER1) and related family members have been shown to transduce extracellular signals through the mitogen-activated protein kinase (MAPK) pathway to regulate post-translational regulation of myocyte enhancer factor 2 (MEF2) proteins. We have previously reported that suppression of MEF2 isoforms in target tumor cells reduced the growth inhibitory effect of RENCA macrobeads. In this study, we evaluated signaling through EGFR in response to RENCA macrobead conditioned media and examined post-translational activation of MEF2D, using the human prostate cancer, DU145 and the human breast adenocarcinoma, MCF7 cell lines. DU145 and MCF7 cells exposed to naive or conditioned media were evaluated using In-Cell Western™ analysis for the expression of phospho-EGFR Y1068 in parallel with total EGFR. Phospho-MEF2D and total MEF2D were assessed in nuclear extracts using western blotting. In the DU145 cells, exposure to RENCA macrobead conditioned media activates EGFR as evidenced by phosphorylation of the receptor at tyrosine 1068 in parallel with the increasing age and inhibitory capacity of macrobeads. Further, the growth inhibition of DU145 cells exposed to RENCA macrobead conditioned media is accompanied by dephosphorylation of MEF2D at Serine 444 supporting a role for increased MEF2D transcriptional activity in the inhibitory effect. MCF7 cells are less sensitive to RENCA macrobead-induced growth inhibition, EGFR is not phosphorylated by 2 hours following exposure to macrobead conditioned media and MEF2D remains phosphorylated at Serine 444. These findings support the hypothesis that RENCA macrobeads signal, at least in part, through the EGF receptor to differentially regulate MEF2D, which is significant for macrobead-induced tumor growth inhibition. Citation Format: Prithy C. Martis, Melissa A. Laramore, Atira Dudley, Barry H. Smith, Lawrence S. Gazda. MEF2 plays a significant role in the tumor inhibitory effects of agarose encapsulated RENCA cells through the EGF receptor. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1675. doi:10.1158/1538-7445.AM2015-1675