D122p53 mice (a model of D133p53 isoform) are tumour prone, have extensive inflammation and elevated serum IL-6. To investigate the role of IL-6 we crossed 122p53 mice with IL-6 deficient mice. Here we show that loss of IL-6 reduced JAK-STAT signalling, tumour incidence, and metastasis. We also show that D122p53 activates RhoA-ROCK signalling leading to tumour cell invasion which is IL-6 dependent and can be reduced by inhibition of JAK-STAT and RhoA-ROCK pathways. Similarly, we show that 133p53 activates the these pathways, resulting in invasive and migratory phenotypes, in colorectal cancer cells. Gene expression analysis of colorectal tumours showed enrichment of GPCR signalling associated with D133TP53 mRNA. Patients with elevated D133TP53 mRNA levels had a shorter disease free survival. Our results suggest that D133p53 promotes tumour invasion by activation of the JAK-STAT and RhoA-ROCK pathways and that patients whose tumours have high D133p53 may benefit from therapies targeting these pathways.
∆133p53 isoform promotes tumour invasion and metastasis via interleukin-6 activation of JAK-STAT and RhoA-ROCK signalling.
Specimen part
View SamplesRad21 is a subunit of cohesin. The main function of cohesin is to hold replicated chromosomes together until cells divide, but it also plays a role in gene expression. To find out which genes might be regulated by cohesin, a study was conducted to look for global changes in gene expression in zebrafish embryos lacking cohesin component Rad21.
Positive regulation of c-Myc by cohesin is direct, and evolutionarily conserved.
Specimen part, Time
View SamplesOur study in zebrafish is the first to use an animal model to understand the biology of the developmental disorder Roberts Syndrome (RBS). RBS is caused by mutations in the ESCO2 gene.
A zebrafish model of Roberts syndrome reveals that Esco2 depletion interferes with development by disrupting the cell cycle.
Age, Specimen part
View SamplesSurgical removal of the lens from larval Xenopus laevis results in a rapid transdifferention of central corneal cells to form a new lens. The trigger for this process is understood to be an induction event arising from the unprecedented contact between the cornea and the vitreous humour that occurs following lens removal. The identity of this trigger is unknown. Here, we have used a functional transgenic approach to show that BMP signalling is required for lens regeneration and a microarray approach to identify genes that are upregulated specifically during this process. Analysis of the array data strongly implicates Wnt signalling and Pitx transcription factors in this process. Pluripotency genes, in contrast, are not upregulated, supporting the idea that corneal cells transdifferentiate without returning to a stem cell state. Furthermore, several genes from the array were expressed in the forming lens during embryogenesis. One of these, nipsnap1, is a known direct target of BMP signalling. We suggest that, as with tail regeneration, activation of multiple developmental signalling pathways could drive lens regeneration from the cornea.
Transdifferentiation from cornea to lens in Xenopus laevis depends on BMP signalling and involves upregulation of Wnt signalling.
Specimen part
View SamplesThe transcription factors PAX3 and MITF are required for the development of the neural crest and melanocyte lineage, and both proteins play important roles in melanoma cell growth and survival. PAX3 transcriptionally activates MITF expression during neural crest development, but the relationship between these transcription factors during melanocyte development and in melanoma cells is currently poorly understood. This study aimed to further our understanding of the interaction between transcriptional networks controlled by PAX3 and MITF by assessing the effect of siRNA-mediated knockdown of PAX3 and MITF in metastatic melanoma cell lines. The goals of this study were to determine (i) if PAX3 is required for maintaining expression of MITF in melanoma and melanocyte cell lines; (ii) whether PAX3 and MITF independently, or redundantly, influence growth and survival in melanoma cell lines; and (iii) to investigate the respective roles of PAX3 and MITF expression in melanoma cell differentiation.
No associated publication
Specimen part, Cell line, Treatment
View SamplesChanges in gene expression on MNV infection of RAW264.7 cells
Murine norovirus replication induces G0/G1 cell cycle arrest in asynchronously growing cells.
Cell line
View SamplesRAW264.7 macrophages infected with MNV-1 and mock infected gene expression measured by microarray.
Characterization of the chemokine response of RAW264.7 cells to infection by murine norovirus.
Specimen part
View SamplesEpimorphic regeneration is the process by which complete regeneration of a complex structure such as a limb occurs through production of a proliferating blastema. This type of regeneration is rare among vertebrates but does occur in the African clawed frog Xenopus laevis, traditionally a model organism for the study of early development. Xenopus tadpoles can regenerate tails, limb buds and the lens of the eye, although the ability of the latter two organs to regenerate diminishes with advancing developmental stage. Using a heat shock inducible transgene that remains silent unless activated, we have established a stable line of transgenic Xenopus in which the BMP inhibitor Noggin can be over-expressed at any time during development. We have previously shown that activation of this transgene blocks regeneration of the tail and limb of Xenopus tadpoles. In the current study, we have taken advantage of this transgenic line to directly compare gene expression in same stage regenerating vs. non-regenerating hind limb buds. Using Affymetrix gene chip analysis, we have identified genes whose expression levels are linked to regenerative success. These include the BMP inhibitor Gremlin and the stress protein Hsp60 (no blastema in zebrafish). Analysis of overrepresented Gene Ontology functional groupings suggests that successful regeneration in the Xenopus hind limb depends on induction of stress response pathways. Furthermore, as expected, genes involved in embryonic development and growth are also significantly over-represented in regenerating early hind limb buds.
Identification of genes associated with regenerative success of Xenopus laevis hindlimbs.
No sample metadata fields
View SamplesGenome-wide association studies have identified a small region at chromosome 9p21.3 strongly associated with coronary heart disease risk. The region contains no protein-coding genes and the mechanism underlying its association with heart disease is unknown. We investigated associations between rs1333049, a single nucleotide polymorphism representing the 9p21.3 locus, and levels of cardiac gene expression in myocardial tissue from donors with no documented history of heart disease.
The chromosome 9p21.3 coronary heart disease risk allele is associated with altered gene expression in normal heart and vascular tissues.
Sex, Age
View SamplesMicroarrays were used to detail the global program of gene expression underlying differences in the organisation of inflammatory cells classified by the expression of the CD21L and IL-17A genes. Synovia were defined by the expression of the CD21L and IL-17A genes as determined by semi-quantitative PCR.
Co-expression of CD21L and IL17A defines a subset of rheumatoid synovia, characterised by large lymphoid aggregates and high inflammation.
Specimen part, Disease, Disease stage, Subject
View Samples