Hypoxia Inducible Factor 1 Confers Androgen Independence in Prostate Cancer
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ABSTRACT:
PROVIDER: PRJNA472393 | ENA |
REPOSITORIES: ENA
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Project description:Hypoxia inducible factor 1 (HIF1) has been shown to cooperate with the androgen receptor (AR) in activation of oncogenic pathways in prostate cancer (PCa). Here we hypothesized that HIF1 also plays a role in PCa response to androgen deprivation therapy (ADT). Comparison of gene expression profiles of androgen exposed (AE) and androgen deprived (AD) CWR22 PCa xenografts identified 596 upregulated and 748 downregulated genes after ADT. Gene ontology (GO) analysis of the differentially expressed genes showed significant enrichment of the biological processes cell proliferation, cell cycle and metabolism and suggested suppression of these processes after ADT. A set of 80 hypoxia-inducible genes were identified in 22Rv1 and LNCaP cell lines treated with hypoxia and showed considerable overlap (53%) with the downregulated genes. Immunostaining of the hypoxia marker pimonidazole showed no difference between AE- and AD-tumors. Comparison of the differentially expressed genes with lists of 1115 direct AR- and 276 direct HIF1-target genes identified 138 AR- and 40 HIF1-targets that were regulated after ADT, including six shared AR- and HIF1-targets for which downregulation was confirmed with RT-PCR. Most HIF1-targets were downregulated and included in the significant biological processes and the set of hypoxia-inducible genes. The downregulation of HIF1-targets was consistent with decreased HIF1A immunostaining in AD- compared to AE-tumors (p=0.002). A decrease in HIF1A immunostaining after ADT was also demonstrated in a cohort of 35 PCa patients (p<0.001). These data suggest suppressed HIF1-signaling after ADT and a shared role of HIF1 and AR in the regressive phase of PCa after ADT. Prostate cancer xenografts were subjected to adrogen deprivation therapy and analysed with regard to changes in gene expressions. Cell culture experiments were performed to generate prostate cancer specific gene lists associated with hypoxia.
2013-10-02 | E-GEOD-42868 | biostudies-arrayexpress
Project description:Hypoxia inducible factor 1 (HIF1) has been shown to cooperate with the androgen receptor (AR) in activation of oncogenic pathways in prostate cancer (PCa). Here we hypothesized that HIF1 also plays a role in PCa response to androgen deprivation therapy (ADT). Comparison of gene expression profiles of androgen exposed (AE) and androgen deprived (AD) CWR22 PCa xenografts identified 596 upregulated and 748 downregulated genes after ADT. Gene ontology (GO) analysis of the differentially expressed genes showed significant enrichment of the biological processes cell proliferation, cell cycle and metabolism and suggested suppression of these processes after ADT. A set of 80 hypoxia-inducible genes were identified in 22Rv1 and LNCaP cell lines treated with hypoxia and showed considerable overlap (53%) with the downregulated genes. Immunostaining of the hypoxia marker pimonidazole showed no difference between AE- and AD-tumors. Comparison of the differentially expressed genes with lists of 1115 direct AR- and 276 direct HIF1-target genes identified 138 AR- and 40 HIF1-targets that were regulated after ADT, including six shared AR- and HIF1-targets for which downregulation was confirmed with RT-PCR. Most HIF1-targets were downregulated and included in the significant biological processes and the set of hypoxia-inducible genes. The downregulation of HIF1-targets was consistent with decreased HIF1A immunostaining in AD- compared to AE-tumors (p=0.002). A decrease in HIF1A immunostaining after ADT was also demonstrated in a cohort of 35 PCa patients (p<0.001). These data suggest suppressed HIF1-signaling after ADT and a shared role of HIF1 and AR in the regressive phase of PCa after ADT.
2013-10-02 | GSE42868 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2019-05-15 | GSE114734 | GEO
Project description:We performed gene expression profiling of oligooxopiperazines (OPs) targeting the hypoxia-inducible transcription factor complex. Treatment of cells with OPs inhibited hypoxia-inducible gene expression in A549 cells.
2013-06-30 | GSE48134 | GEO
Project description:High levels of GLI (GLI1 and GLI2) mRNA and GLI luciferase reporter activity were detected in the androgen independent prostate cancer cell lines DU145 and PC-3 compared to the androgen-dependent LNCaP prostate cancer cell line. Subsequently, we observed that ectopic GLI1 promoted hormone independence in LNCaP cells (LNCaP-GLI1). We compared the gene expression profile of LNCaP-pBP (empty vector), LNCaP-GLI1, DU145, and PC-3 cells globally as well as to identify GLI1-regulated genes that may contribute to hormone independence. RNA was harvested and analysed from LNCap-pBP (control/reference sample), LNCaP-GLI1, DU145 and PC-3 cells
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Project description:Hypoxia-inducible transcription factors (HIFs) are crucial transcription factors for cellular response to low oxygen levels, but the key mediators for their downstream transcription activation are not well characterized. We previously found that PRMT2 activates target gene expression through its methyltransferase activity on histone H3R8. Here we find that PRMT2 expression is activated by HIF1 at hypoxic conditions. And PRMT2 activity is widely required for hypoxia-induced transcription activation. Accordingly, PRMT2 inactivation alleviates hypoxia-induced glioblastoma progression and chemotherapeutic resistance. And PRMT2 expression is associated with hypoxia signature
2024-04-01 | GSE235438 | GEO
Project description:High levels of GLI (GLI1 and GLI2) mRNA and GLI luciferase reporter activity were detected in the androgen independent prostate cancer cell lines DU145 and PC-3 compared to the androgen-dependent LNCaP prostate cancer cell line. Subsequently, we observed that ectopic GLI1 promoted hormone independence in LNCaP cells (LNCaP-GLI1). We compared the gene expression profile of LNCaP-pBP (empty vector), LNCaP-GLI1, DU145, and PC-3 cells globally as well as to identify GLI1-regulated genes that may contribute to hormone independence.
2011-02-13 | GSE27231 | GEO
Project description:Androgen and hypoxia are two cancer hallmark pathways; both exert biological effects primarily via the regulation of gene expression We used gene expression array to determine the global gene expression changes due to androgen, castration (androgen-free) in normoxia and hypoxia conditions. Microarray assays were performed in the OHSU Gene Profiling Shared Resource
2018-10-30 | GSE120343 | GEO
Project description:We performed gene expression profiling of hydrogen-bond surrogate that targets hypoxia-inducible transcription factior complex and results in inhibition of hypoxia-inducible genes with relatively minimal perturbation of non-targeted signaling pathways.
2013-06-18 | GSE48002 | GEO