Activation of the hypoxia inducible transcription factor HIF-alpha and the NF-kappaB pathway promotes inflammation mediated tumor progression.
The hypoxia-inducible transcription factor ZNF395 is controlled by IĸB kinase-signaling and activates genes involved in the innate immune response and cancer.
Cell line, Treatment
View SamplesIn cervical cancer, an important mechanism by which tumour cells escape immune surveillance is loss of HLA class I, enabling tumours to evade recognition and lysis by cytotoxic T lymphocytes. Some tumours, however, escape from immune surveillance without accumulating defects in antigen presentation. We hypothesized that tumours with no or partial loss of HLA class I develop alternative mechanisms to prevent immune surveillance. To investigate this hypothesis, genome-wide expression profiling using Illumina arrays was performed on cervical squamous cell carcinomas showing overall loss of HLA class I, partial and normal HLA class I protein expression. Statistical analyses revealed no significant differences in gene expression between tumours with partial (n = 11) and normal HLA class I expression (n = 10). Comparison of tumours with normal/partial HLA class I expression (n = 21) with those with overall loss of HLA class I expression (n = 11) identified 150 differentially expressed genes. Most of these genes were involved in the defense response (n = 27), and, in particular, inflammatory and acute phase responses. Especially SerpinA1 and SerpinA3 were found to be upregulated in HLA positive tumours (3.6 and 8.2 fold, respectively), and this was confirmed by real-time PCR and immunohistochemistry. In a group of 117 tumours, high SerpinA1 and SerpinA3 expression in association with normal/partial HLA expression correlated significantly with poor overall survival (p = 0.035 and p = 0.05, respectively). This study shows that HLA positive tumours are characterized by a higher expression of genes associated with an inflammatory profile and that expression of the acute phase proteins SerpinA1 and SerpinA3 in HLA positive tumours is associated with worse prognosis.
Elevated expression of SerpinA1 and SerpinA3 in HLA-positive cervical carcinoma.
No sample metadata fields
View SamplesRNA-seq analysis was performed using RNA isolated from three tumor models (GL261 glioma, LLC Lewis lung carcinoma, B16F10 melanoma) implanted subcutaneousy in C57BL/6 mice, or in ICR scid mice. Mice were untreated or were treated with cyclophosphamide (CPA) given on a 6-day repeating metronomic schedule (CPA/6d), except as noted. Results from these global transcriptome analysis indicated substantial elevation of basal GL261 immune infiltration and strong activation by CPA/6d treatment of GL261 immune stimulatory pathways and their upstream regulators, but without preferential depletion of negative immune regulators compared to LLC and B16F10 tumors. In LLC tumors, where CPA/6d treatment was found to be anti-angiogenic, CPA/6d suppressed VEGFA target genes and down regulated cell adhesion and leukocyte transendothelial migration genes. In GL261 tumors implanted in adaptive immune-deficient scid mice, where CPA/6d-induced GL261 regression is incomplete and late tumor growth rebound can occur, T cell receptor signaling and certain cytokine-cytokine receptor responses seen in B6 mice were deficient. Extending the CPA treatment interval from 6 to 9 days (CPA/9d) - which results in a strong but transient natural killer cell response followed by early tumor growth rebound - induced fewer cytokines and increased expression of drug metabolism genes. Taken together, these findings elucidate molecular response pathways activated by intermittent metronomic CPA treatment and identify deficiencies that characterize immune-unresponsive tumor models and drug schedules. Overall design: RNA isolated from various tumor cell lines implanted s.c in C57BL/6 mice or scid mice, untreated or treated with cyclophosphamide (CPA) given on a metronomic schedule, were prepared and used for stranded or unstranded RNA-seq.
Metronomic cyclophosphamide activation of anti-tumor immunity: tumor model, mouse host, and drug schedule dependence of gene responses and their upstream regulators.
No sample metadata fields
View SamplesThe use of statistical tools established for the genetic analysis of quantitative traits can be applied to gene expression data. Quantitative trait loci (QTL) analysis can associate expression of genes or groups of genes with particular genomic regions and thereby identify regions that play a role in the regulation of gene expression. A segregating population of 41 doubled haploid (DH) lines from the hard red spring wheat cross RL4452 x AC Domain was used. This population had previously been mapped with microsatellites and includes a full QTL analysis for agronomic and seed quality traits. Expression analysis from 5 day post anthesis developing seed was conducted on 39 of the 41 DH lines using the Affymetrix wheat array. Expression analysis of developing seeds from field grown material identified 1,327 sequences represented by Affymetrix probe sets whose expression varied significantly between genotypes of the population. A sub-set of 378 transcripts were identified that each mapped to a single chromosome interval illustrating that major expression QTLs can be found in wheat. Genomic regions corresponding to multiple expression QTLs were identified that were coincident with previous identified seed quality trait QTL. These regions may be important regulatory regions governing economically important traits. Comparison of expression mapping data with physical mapping for a sub-set of sequences showed that both cis and trans acting expression QTLs were present.
Identifying regions of the wheat genome controlling seed development by mapping expression quantitative trait loci.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Identifying regions of the wheat genome controlling seed development by mapping expression quantitative trait loci.
No sample metadata fields
View SamplesThe use of statistical tools established for the genetic analysis of quantitative traits can be applied to gene expression data. Quantitative trait loci (QTL) analysis can associate expression of genes or groups of genes with particular genomic regions and thereby identify regions that play a role in the regulation of gene expression. A segregating population of 41 doubled haploid (DH) lines from the hard red spring wheat cross RL4452 x AC Domain was used. This population had previously been mapped with microsatellites and includes a full QTL analysis for agronomic and seed quality traits. Expression analysis from 5 day post anthesis developing seed was conducted on 36 of the 41 DH lines using the Affymetrix wheat array. Expression analysis of developing seeds from field grown material in location 2 identified 10,280 sequences represented by Affymetrix probe sets whose expression varied significantly between genotypes of the population. Of these 1,455 were identified in the point location as well. A sub-set of 542 transcripts were identified that each mapped to a single chromosome interval illustrating that major expression QTLs can be found in wheat. Genomic regions corresponding to multiple expression QTLs were identified that were coincident with previous identified seed quality trait QTL. These regions may be important regulatory regions governing economically important traits. Comparison of expression mapping data with physical mapping for a sub-set of sequences showed that both cis and trans acting expression QTLs were present.
Identifying regions of the wheat genome controlling seed development by mapping expression quantitative trait loci.
No sample metadata fields
View SamplesThe use of statistical tools established for the genetic analysis of quantitative traits can be applied to gene expression data. Quantitative trait loci (QTL) analysis can associate expression of genes or groups of genes with particular genomic regions and thereby identify regions that play a role in the regulation of gene expression. A segregating population of 41 doubled haploid (DH) lines from the hard red spring wheat cross RL4452 x AC Domain was used. This population had previously been mapped with microsatellites and includes a full QTL analysis for agronomic and seed quality traits. Expression analysis from 5 day post anthesis developing seed was conducted on 39 of the 41 DH lines using the Affymetrix wheat array. Expression analysis of developing seeds from field grown material identified 1,327 sequences represented by Affymetrix probe sets whose expression varied significantly between genotypes of the population. A sub-set of 378 transcripts were identified that each mapped to a single chromosome interval illustrating that major expression QTLs can be found in wheat. Genomic regions corresponding to multiple expression QTLs were identified that were coincident with previous identified seed quality trait QTL. These regions may be important regulatory regions governing economically important traits. Comparison of expression mapping data with physical mapping for a sub-set of sequences showed that both cis and trans acting expression QTLs were present.
Identifying regions of the wheat genome controlling seed development by mapping expression quantitative trait loci.
No sample metadata fields
View SamplesThe use of statistical tools established for the genetic analysis of quantitative traits can be applied to gene expression data. Quantitative trait loci (QTL) analysis can associate expression of genes or groups of genes with particular genomic regions and thereby identify regions that play a role in the regulation of gene expression. A segregating population of 41 doubled haploid (DH) lines from the hard red spring wheat cross RL4452 x AC Domain was used. This population had previously been mapped with microsatellites and includes a full QTL analysis for agronomic and seed quality traits. Expression analysis from 5 day post anthesis developing seed was conducted on 36 of the 41 DH lines using the Affymetrix wheat array. Expression analysis of developing seeds from field grown material in location 2 identified 10,280 sequences represented by Affymetrix probe sets whose expression varied significantly between genotypes of the population. Of these 1,455 were identified in the point location as well. A sub-set of 542 transcripts were identified that each mapped to a single chromosome interval illustrating that major expression QTLs can be found in wheat. Genomic regions corresponding to multiple expression QTLs were identified that were coincident with previous identified seed quality trait QTL. These regions may be important regulatory regions governing economically important traits. Comparison of expression mapping data with physical mapping for a sub-set of sequences showed that both cis and trans acting expression QTLs were present.
Identifying regions of the wheat genome controlling seed development by mapping expression quantitative trait loci.
No sample metadata fields
View SamplesAt least six histone H1 variants exist in mammalian somatic cells that bind to the linker DNA and stabilize the nucleosome particle contributing to higher order chromatin compaction. In addition, H1 seems to be involved in the active regulation of gene expression. It is not well known whether the different variants have specific roles or regulate specific promoters. We have explored this by inducible shRNA-mediated knock-down of each of the H1 variants in a human breast cancer cell line. A different subset of genes is altered in each H1 knock-down.
Depletion of human histone H1 variants uncovers specific roles in gene expression and cell growth.
No sample metadata fields
View SamplesAfter-ripening induced seed dormancy release in wheat is associated with mRNA oxidation.
Integrated analysis of seed proteome and mRNA oxidation reveals distinct post-transcriptional features regulating dormancy in wheat (Triticum aestivum L.).
Specimen part
View Samples