BioProject

Cancer patients after successful therapy contain nested in their organs and/or circulating in the systemic fluids tumor cells that remain asymptomatic for an extended period of time. More...

Cancer patients after successful therapy contain nested in their organs and/or circulating in the systemic fluids tumor cells that remain asymptomatic for an extended period of time. They stay dormant with no apparent immediate potential to develop into a clinically manifested tumor until activated by yet not well defined mechanisms. In the present study, we developed tumor dormancy model of murine melanoma, a cancer with a high potential of phenotype plasticity to adapt to micro-environmental changes, in which to investigate cellular quiescence and related factors as a potential mechanism of tumour dormancy. To explore molecular mechanism responsible for cellular dormancy, we performed a comparative transcriptome analysis of dormant B16F1-GFP-D and maternal B16F1-GFP-M cells. Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a nuclear receptor highly expressed by colonic epithelial cells. It plays a key role in gut homeostasis and metabolism regulation. We previously showed that PPARgamma has a role in the action of aminosalycilates (5-ASA), one of the oldest anti-inflammatory agents used in the treatment of inflammatory bowel disease. These data have prompted us to develop novel analogues of 5-ASA with greater PPARgamma-activating properties (GED). The various PPARgamma ligands appear to have some markedly different effects, some of which can induce adverse effects. The transcriptomic profiles induced by various families of PPARgamma ligands are very poorly known and especially in intestinal epithelial cells. Hence, the objectives of the present project are to compare the gene expression profile induced by GED, 5-ASA, and pioglitazone in Caco-2 cells, in order to better understand these compounds’ modes of action, to discover potential new PPARgamma target genes in intestinal epithelial cells and to explain the efficacy difference between GED and 5-ASA. Overall design: 1 million of B16F1-GFP-M and B16F1-GFP-D melanoma cells were cultured in DMEM 10% FBS medium. The cells were rinsed twice with sterile PBS. Total RNA extraction was performed following the manufacturer's protocol (RNeasy Kit, Qiagen, Courtaboeuf, France) with optional DNase treatment. Less...