Background: Genes upregulated by low oxygen have been suggested as endogenous markers for tumor hypoxia. Yet, most of the genes investigated have shown inconsistent results, which have led to concerns about their ability to be true hypoxia markers. Previous studies have demonstrated that expression of hypoxia induced genes can be affected by extracellular pH (pH e ). Methods: Five different human cell lines (SiHa, FaDu DD, UTSCC5, UTSCC14 and UTSCC15) were exposed to different oxygen concentrations and pH (7.5 or 6.3), and gene expression analyzed with microarray (Affymetrix - Human Genome U133 Plus 2.0 Array). Results: An analysis of two of the cell lines using SAM identified 461 probesets that were able to separate the four groups Normal oxygen, normal pH , Low oxygen, normal pH , Normal oxygen, low pH and Low oxygen, low pH . From here it was possible to identify a fraction of probesets induced at low oxygen independent of pH in these two cell lines, this fraction included HIG2, NDRG1, PAI1 and RORA. Further verifi cation by qPCR highlighted the necessity of using more cell lines to obtain a robust gene expression profi les. To specifi cally select pH independent hypoxia regulated genes across more cell lines, data for FaDu DD, UTSCC5, UTSCC14 and UTSCC15 were analyzed to identify genes that were induced by hypoxia in each cell line, where the induction was not affected by low pH, and where the gene was not signifi cantly induced by low pH alone. Each cell line had 65 122 probesets meeting these criteria. For genes to be considered as target genes (hypoxia inducible pH independent), genes had to be present in three of four cell lines. Conclusion: The result is a robust hypoxia profile unaffected by pH across cell lines consisting of 27 genes. This study demonstrates a way to identify hypoxia markers by microarray, where other factors in the tumor microenvironment are taken into account.
Identifying pH independent hypoxia induced genes in human squamous cell carcinomas in vitro.
Cell line
View SamplesGene expression in eukaryotes is an essential process that includes transcription, pre-RNA processing and RNA export. All these steps are coupled and normally, any failure in one step affects the other steps and could cause nuclear mRNA retention. One important player in this interface is the poly(A)-RNA binding protein Nab2, which regulates the poly(A)-tail length of mRNAs protecting their 3-ends from a second round of polyadenylation and facilitating their nucleo-cytoplasmic export. Interestingly, here we show that Nab2 has additional roles in mRNA transcription elongation, tRNA metabolism and rRNA export.
Nab2 functions in the metabolism of RNA driven by polymerases II and III.
No sample metadata fields
View SamplesGene expression in eukaryotes is an essential process that includes transcription, pre-RNA processing and RNA export. All these steps are coupled and normally, any failure in one step affects the other steps and could cause nuclear mRNA retention. One important player in this interface is the poly(A)-RNA binding protein Nab2, which regulates the poly(A)-tail length of mRNAs protecting their 3-ends from a second round of polyadenylation and facilitating their nucleo-cytoplasmic export. Interestingly, here we show that Nab2 has additional roles in mRNA transcription elongation, tRNA metabolism and rRNA export.
Nab2 functions in the metabolism of RNA driven by polymerases II and III.
No sample metadata fields
View SamplesWe report a new protein complex with a role in transcription elongation that is formed by Ypr045c (Thp3) and the Csn12 component of the COP9-signalosome. Thp3-Csn12 is recruited to transcribed genes. Their mutations suppress the gene expression defects of mutants of the THO complex involved in mRNP biogenesis and export and show defects in mRNA accumulation. In vivo transcription elongation impairment of thp3 mutants is shown by reduction of RNAPII recruitment throughout an active gene and in transcript run on analysis performed in G-less systems. This new complex establishes a novel link between transcription and mRNA processing.
New suppressors of THO mutations identify Thp3 (Ypr045c)-Csn12 as a protein complex involved in transcription elongation.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Post-transplant molecularly defined Burkitt lymphomas are frequently MYC-negative and characterized by the 11q-gain/loss pattern.
Sex, Age, Treatment
View SamplesWe performed genomic and transcriptomic analysis of seven cases of molecular Burkitt lymphoma (mBL) developed in immunosuppressed patients who underwent solid organ transplantation. Interestingly, three cases (43%) were MYC-translocation-negative and revealed the 11q-gain/loss aberration recently identified in 3% of mBL developed in immunocompetent hosts.1 Based on array CGH data, minimal gain and loss regions of 11q (MGR/~4Mb and MLR/~13.5Mb, respectively) were defined and integrative genomic and transcriptomic analysis identified 35 differentially expressed genes, when compared with classic BL. All 16 MGR-dysregulated genes were upregulated, including cancer related USP2, CBL and PAFAH1B2. As expected, all 19 MGL-dysregulated genes were downregulated and two of them, TBRG1 and EI24, are potential tumor suppressor genes. Interestingly, the vast majority of dysregulated 11q23-q25 genes are involved in the MYC and TP53 networks. We hypothesize that the 11q-gain/loss aberration represents a molecular variant of t(8q24/MYC) and affects the same pathological pathways as the MYC oncogene.
Post-transplant molecularly defined Burkitt lymphomas are frequently MYC-negative and characterized by the 11q-gain/loss pattern.
Sex, Age, Treatment
View SamplesIn a supervised principal component analysis, histiocytes from TCHRBCL were most closely related to epithelioid cells from NLPHL, with both types of cells expressing genes related to proinflammatory and regulatory macrophage activity.
Macrophages in T cell/histiocyte rich large B cell lymphoma strongly express metal-binding proteins and show a bi-activated phenotype.
Specimen part
View SamplesT-cell/histiocyte rich B cell lymphoma (THRBL) and nodular lymphocyte predominant Hodgkin's lymphoma (NLPHL) share some morphological characteristics, including a prominent stromal reaction, but display a markedly different prognosis. To investigate the difference between the stromal reactions of these lymphomas at the molecular level, we performed microarray expression profiling on a series of THRBL and NLPHL cases.
T-cell/histiocyte-rich large B-cell lymphoma shows transcriptional features suggestive of a tolerogenic host immune response.
Sex, Specimen part
View SamplesIn this study we focussed on malignant post-transplant lymphomas.
Gene expression profiling reveals clear differences between EBV-positive and EBV-negative posttransplant lymphoproliferative disorders.
Specimen part
View SamplesTumor cells were microdissected from frozen sections of NLPHL and THRLBCL. RNA was amplified using the NUGEN WT-Ovation-One-direct-Kit. Samples were compared to tonsilar germinal center CD77 B cells.
Nodular lymphocyte predominant hodgkin lymphoma and T cell/histiocyte rich large B cell lymphoma--endpoints of a spectrum of one disease?
Specimen part
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