Project description:We report different transcriptional profiles of WT, p53-/- and p53R172H cells derived from mouse esophagi. P53-/- and p53R172H expressing mice were treated with 4NQO to enhance tumor formation.
Project description:Transcriptional profiling of Esophageal Squamous Cell Carcinoma (ESCC) tumors comparing samples harbouring nuclear-stabilized p53 (NS+) versus unstable p53 (NS-) protein, determined through immunohistochemistry (IHC) staining of the tumor sections. The goal was to identify the genes that were differentially regulated between NS+ and NS- ESCC samples.
Project description:Microarray expression data generated to determine the impact of defined p53 mutations on lung cancer cell phenotypes, and on the tumour supressive responses induced by WT p53 restoration. In murine models of lung cancer, the therapeutic benefit of WT p53 restoration has been demonstrated in p53-deficient tumours (Juntilla et al, 2010; Feldser et al, 2010). However, it remains unknown if the restoration of WT p53 function is beneficial in p53 mutant tumours. Thus, to determine the impact of p53-targeted therapy in mutant p53 lung cancer, we analysed cells from murine lung tumours of distinct p53 genotypes. Utilising the well characterised p53-ER allele (Christophorou et al, 2005; Martins et al, 2006; Juntilla et al, 2010) we carried out transcriptional profiling of KrasG12D/+ cell lines isolated from advanced lung tumours with defined p53 status: p53Fx/ER (null), p53R270H/ER and p53R172H/ER in the absence (p53 WT OFF) or presence (p53 WT ON) of 4-hydroxytamoxifen (4-OHT). The temporal specificity of p53-ER restoration allowed us to utilised two timepoints to determine both the immediate (2hr) and sustained (8hr) impact of WT p53 function.
Project description:Transcriptional profiling of mouse esophageal development. Goal was to globally profile critical genes and signaling pathways during the development of mouse esophagus and determine how Nrf2/Keap1 pathway regulates the morphogenesis of the esophageal epithelium. Mutiple-comparison. WT-E11.5 vs. WT-E15.5 vs. WT-P0 vs. WT-P7; WT-P7 vs. WT-adult; WT-adult vs. Nrf2-/--adult; WT-P7 vs. Nrf2-/--P7 vs. Keap1-/--P7 vs. Nrf2-/-Keap1-/--P7. Biological replicates: 3 replicates for each group.
Project description:Transcriptional profiling of H1299 non-small cell lung carcinoma cells transfected with either wt p53 or mut(175) p53 driven by the 5xHRE promoter (5 repeats of hypoxia-inducible factor response elements) and treated for 16 h with normoxia (21% O2) or hypoxia(<0.1% O2). 5xHRE promoter ensures that p53 expression is induced in hypoxic conditions only. Goal was to determine the transcriptional response of p53 in hypoxia and the 175 p53 mutant was used as a control as it is DNA-binding defective and transcription-incompetent mutant. Four-condition experiment: wt p53-transfected H1299 cells treated with normoxia, mut p53-transfected H1299 cells treated with normoxia, wt p53-transfected H1299 cells treated with hypoxia, mut p53-transfected H1299 cells treated with hypoxia. Biological replicates: 1 normoxic sample with wt p53, 1 normoxic sample with mut p53, 3 hypoxic samples with wt p53, 3 hypoxic samples with mut p53.
Project description:The iTRAQ-based proteome profile was also identified in the mutant and WT to provide a deeper insight into post-transcriptional modifications.
Project description:Transcriptional profiling of H1299 non-small cell lung carcinoma cells transfected with either wt p53 or mut(175) p53 driven by the 5xHRE promoter (5 repeats of hypoxia-inducible factor response elements) and treated for 16 h with normoxia (21% O2) or hypoxia(<0.1% O2). 5xHRE promoter ensures that p53 expression is induced in hypoxic conditions only. Goal was to determine the transcriptional response of p53 in hypoxia and the 175 p53 mutant was used as a control as it is DNA-binding defective and transcription-incompetent mutant.
Project description:MicroRNAs (miRNAs) are an endogenous conserved class of non-coding 20–22 nt small RNAs that regulate gene expression at post-transcriptional level by mostly binding to 3′-UTR of target mRNAs, leading to mRNA degradation or translation inhibition. Recent reports demonstrate a role for miRNA expression in the disease progression and outcome. By now, many researcher focusing on miRNA expression profiles in Barrett's esophagus and esophageal adenocarcinoma have been reported. Nevertheless, there is still a little information available about specific miRNA expression pattern and their roles in ESCC. To develop novel diagnostic and therapeutic targets for esophageal squamous cancer, we first investigated the expression profile of miRNA in three pairs of ESCC clinical samples.
Project description:Transcriptional profiling of mouse esophageal development. Goal was to globally profile critical genes and signaling pathways during the development of mouse esophagus and determine how Nrf2/Keap1 pathway regulates the morphogenesis of the esophageal epithelium.
Project description:Gene expression profiling was determined in BAMC isolated from non-irradiated and irradiated p53-null and p53-WT mice. We selected strongly expressed genes in p53-WT compared to p53-null BAMC. They belonged to different pathways.Also, a number of genes coded secreting proteins that , probably, were responsible for the improved hematopoiesis in p53-null mice.