Abstract B36: RENCA macrobead-induced AKT hyperphosphorylation leads to MEF2 activation and inhibition of the proliferation of human DU145 prostate carcinoma cells

We have previously reported that suppression of the isoforms of myocyte enhancer factor (MEF2) in target tumor cells in vitro reduces the demonstrated proliferation-inhibitory effect of agarose-agarose encapsulated mouse renal adenocarcinoma cells (RENCA macrobeads), suggesting that it is a critical component of a pathway by which the inhibitory action, now being evaluated also in Phase IIb human clinical trials, is mediated. Importantly, MEF2 originally described as active in myogenesis, has been found to be a key regulator of many developmental pathways and to have both pro- and anti-growth regulatory functions in murine and human tumor cells.Recent studies have supported a molecular intersection between components of the PI3K/Akt and the canonical Wnt signaling (carcinogenic) pathways, converging at the glycogen synthase kinase 3β (GSK3β) node. In skeletal and cardiac muscle cells, GSK3β regulates MEF2 activity indirectly through reciprocal regulation of the p38 mitogen-activated protein kinase (MAPK) pathway.To determine, therefore, whether PI3K/Akt is also involved in the anti-proliferative effect of the RENCA macrobeads, we evaluated signaling through PI3K/Akt in response to macrobead-conditioned media and examined post-translational modification of MEF2D in two human cell lines DU145 (prostate cancer) and MCF7 (breast adenocarcinoma). Using In-Cell Western analysis, we determined the expression of phospho-Akt T308 and S473 in parallel with total Akt in c...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Other Topics: Poster Presentations - Proffered Abstracts Source Type: research