Expression Proteomics Predicts Loss of RXR-γ during Progression of Epithelial Ovarian Cancer

The process of cellular transformation involves cascades of molecular changes that are modulated through altered epigenetic, transcription, post-translational and protein regulatory networks. Thus, identification of transformation-associated protein alterations can provide an insight into major regulatory pathways activated during disease progression. In the present protein expression profiling approach, we identified differential sets of proteins in a two-dimensional gel electrophoresis screen of a serous ovarian adenocarcinoma progression model. Function-based categorization of the proteins exclusively associated with pre-transformed cells identified four cellular processes of which RXR-gamma is known to modulate cellular differentiation and apoptosis. We thus probed the functional relevance of RXR-gamma expression and signaling in these two pathways during tumor progression. RXR-gamma expression was observed to modulate cellular differentiation and apoptosis in steady-state pre-transformed cells. Interestingly, retinoid treatment was found to enhance RXR-gamma expression in transformed cells and sensitize them towards apoptosis in vitro, and also reduce growth of xenografts derived from transformed cells. Our findings emphasize that loss of RXR-gamma levels appears to provide mechanistic benefits to transformed cells towards the acquisition of resistance to apoptosis hallmark of cancer, while effective retinoid treatment may present a viable approach towards sensitization of tumor cells to apoptosis through induction of RXR-gamma expression.