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Gene expression analysis in primary human renal tumors, categorized by VHL genotype and HIF-alpha expression

ABSTRACT: Human renal cell carcinomas (RCC) have differential expression of HIF-1alpha and HIF-2alpha, depending on VHL genotype and other events. Here, we have divided a series of RCC samples for HIF-alpha expression and VHL genotype, in order to define differentially expressed genes Keywords: Patient Sample Study

ORGANISM(S): Homo sapiens

PROVIDER: GSE11904 | GEO | 2008/12/27

SECONDARY ACCESSION(S): PRJNA105743

REPOSITORIES: GEO

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Gene expression analysis in primary human renal tumors, categorized by VHL genotype and HIF-alpha expression

Project description:Human renal cell carcinomas (RCC) have differential expression of HIF-1alpha and HIF-2alpha, depending on VHL genotype and other events. Here, we have divided a series of RCC samples for HIF-alpha expression and VHL genotype, in order to define differentially expressed genes Keywords: Patient Sample Study A total of 57 frozen RCC samples were stained for HIF-1alpha and HIF-2alpha, and genotyped for VHL. 5 VHL WT/HIF-negative, 8 VHL-deficient/HIF-1alpha+/HIF-2alpha+ and 8 VHL-deficient/HIF-2alpha+ tumors were selected for microarray

2008-12-27 | E-GEOD-11904 | biostudies-arrayexpress

Array CGH analysis in primary human renal tumors, categorized by VHL genotype and HIF-alpha expression

Project description:Human renal cell carcinomas (RCC) have differential expression of HIF-1alpha and HIF-2alpha, depending on VHL genotype and other events. Here, we have divided a series of RCC samples based on HIF-alpha expression, in order to examine levels of genomic DNA aberration. Keywords: Patient Sample Study A total of 57 frozen RCC samples were stained for HIF-1alpha and HIF-2alpha, and genotyped for VHL. 10 VHL-deficient/HIF-1alpha+/HIF-2alpha+ and 11 VHL-deficient/HIF-2alpha+ tumors were selected for array CGH.

2008-12-27 | E-GEOD-13282 | biostudies-arrayexpress

Array CGH analysis in primary human renal tumors, categorized by VHL genotype and HIF-alpha expression

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HIF-2alpha Knockdown in A498 (VHL-/-) ccRCC cells

Project description:HIF-2alpha is essential for (VHL-/-) ccRCC subcutaneous tumor growth in mice, and in tumor cell lines, its inhibition results in increased ROS accumulation, tumor cell death and responsiveness to radiation treatment. We have utilized transcriptional profiling to screen for putative HIF-2alpha targets genes that serve an anti-oxidant and, thus, cell survival function. A498 ccRCC cell line was treated with control siRNA or mixture of two HIF-2alpha specific siRNA for 48 hours, and RNA was harvested. 4 independent experiments were performed, and expression was compared between control and HIF-2alpha knockdown groups.

2009-08-27 | GSE16622 | GEO

HIF-2alpha Knockdown in A498 (VHL-/-) ccRCC cells

2009-08-27 | E-GEOD-16622 | biostudies-arrayexpress

HIF-1alpha and HIF-2alpha ChIP-chip profiling in intestinal epithelial cells

Project description:Intestinal epithelia exist in a uniquely dynamic oxygen tension microenvironment. Adaptive responses to hypoxia in mammalian cells are regulated largely by hypoxia inducible factor (HIF) transcriptional complexes. Functional HIF exists as an obligate alpha/beta heterodimer, comprising both a constitutive subunit (HIF-1beta), and an oxygen-labile regulatory (alpha) component. To date, three regulatory subunits have been identified, namely HIF-1alpha, HIF-2alpha, and HIF-3alpha, with the highest level of sequence homology conserved between HIF-1alpha and HIF-2alpha. Despite their concurrent expression in intestinal epithelial cells, HIF-1 and HIF-2 play non-redundant roles in the regulation of an overlapping but distinct set of gene targets. In this study, we performed ChIP-on-chip analysis of chromatin isolated from hypoxic intestinal epithelia to delineate HIF-1 and HIF-2 specific loci. Comparison of HIF-1alpha ChIP-chip and HIF-2alpha ChIP-chip to map HIF-1- and HIF-2-specific gene targets across the genome.

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Transcription profiling of HIF dependent and independent effects of VHL inactivation in C. elegans

Project description:The von Hippel-Lindau (VHL) tumor suppressor functions as a ubiquitin ligase that mediates proteolytic inactivation of hydroxylated a subunits of hypoxia-inducible factor (HIF). Although studies of VHL defective renal carcinoma cells suggest the existence of other VHL tumor suppressor pathways, dysregulation of the HIF transcriptional cascade has extensive effects that make it difficult to distinguish whether, and to what extent, observed abnormalities in these cells represent effects on pathways distinct from HIF. Here, we report on a genetic analysis of HIF dependent and independent effects of VHL inactivation by studying gene expression patterns in C. elegans. We show tight conservation of the HIF-1/VHL-1/EGL-9 hydroxylase pathway. However, persisting differential gene expression in hif-1 versus hif-1; vhl-1 double mutant worms clearly distinguished HIF-1 independent effects of VHL-1 inactivation. Genomic clustering, predicted functional similarities, and a common pattern of dysregulation in both vhl-1 worms and a set of mutants (dpy-18, let-268, gon-1, mig-17 and unc-6), with different defects in extracellular matrix formation, suggest that dysregulation of these genes reflects a discrete HIF-1 independent function of VHL-1 that is connected with extracellular matrix function.

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Gene expression analysis in renal cell carcinoma

Project description:Renal cell carcinoma (RCC) tumors express varying gene profiles, dependent on VHL and HIF status, as well as other events. Here we analyzed a series of RCC tumors for HIF-alpha expression and VHL genotype, in relation to overal gene expression profiles. Keywords: Patient sample study

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Genome-wide identification of HIF-1 and HIF-2 binding sites in hypoxic human macrophages alternatively activated by IL-10

Project description:Primary human macrophages with a HIF-1alpha or HIF-2alpha knockdown were pretreated with IL-10 for 16h and afterwards for 4h additionaly under hypoxi (1% O2), RNA was isolated usind the Qiagen RNAeasy Kit and cDNA synthesis wos done using Ambion WT Expression Kit. Expression was compared to si control under control conditions.

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