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-γ is known to modulate cellular differentiation and apoptosis. We thus probed the functional relevance of RXR-γ expression and signaling in these two pathways during tumor progression. RXR-γ expression was observed to modulate cellular differentiation and apoptosis in steady-state pre-transformed cells. Interestingly, retinoid treatment was found to enhance RXR-γ 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-γ 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-γ expression.
National Centre for Cell Science, NCCS Complex, Pune University Campus, Ganeshkhind, Pune, Maharashtra, India.
Rajkumar S
RS
Kalra
Sharmila A
SA
Bapat
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D000077216:Carcinoma, Ovarian Epithelial; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D018450:Disease Progression; D020869:Gene Expression Profiling; D063990:Gene Ontology; D008297:Male; D051379:Mice; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D040901:Proteomics; D047491:Retinoid X Receptor gamma / Q000378:metabolism*; D012176:Retinoids / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
D047491:Retinoid X Receptor gamma; D012176:Retinoids