Rattus norvegicus
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ABSTRACT:
PROVIDER: PRJNA219400 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Pheochromocytomas and paragangliomas (PPGLs) are catecholamine-producing tumors with diverse phenotypic features reflecting mutations in numerous genes, including MYC-associated factor X (MAX). To establish whether PPGL phenotypic differences reflect a MAX-mediated mechanism and opposing influences of HIF2α and HIF1α, we combined observational investigations in PPGLs and gene-manipulation studies in two pheochromocytoma cell lines. In cell lines lacking Max, re-expression of the gene resulted in maturation of phenotypic features and decreased cell cycle progression. In cell lines lacking Hif2α, overexpression of the gene led to immature phenotypic features, failure of dexamethasone to induce differentiation and increased proliferation. HIF1α has opposing actions to HIF2α. These model systems explain the features observed in PPGLs due to mutations of MAX and other PPGL susceptibility genes. PC12 cell lines were cultured, one transfected with an emply vector (PC12wt) and the other transfected with an expression plasmid coding the MAX gene. In total four samples were hybridized, each experimental condition had two biological replicates obtained at two different cell passages (8 and 13).
2014-09-18 | E-GEOD-50941 | biostudies-arrayexpress
Project description:Pheochromocytomas and paragangliomas (PPGLs) are catecholamine-producing tumors with diverse phenotypic features reflecting mutations in numerous genes, including MYC-associated factor X (MAX). To establish whether PPGL phenotypic differences reflect a MAX-mediated mechanism and opposing influences of HIF2α and HIF1α, we combined observational investigations in PPGLs and gene-manipulation studies in two pheochromocytoma cell lines. In cell lines lacking Max, re-expression of the gene resulted in maturation of phenotypic features and decreased cell cycle progression. In cell lines lacking Hif2α, overexpression of the gene led to immature phenotypic features, failure of dexamethasone to induce differentiation and increased proliferation. HIF1α has opposing actions to HIF2α. These model systems explain the features observed in PPGLs due to mutations of MAX and other PPGL susceptibility genes.
2014-09-18 | GSE51081 | GEO
Project description:Pheochromocytomas and paragangliomas (PPGLs) are catecholamine-producing tumors with diverse phenotypic features reflecting mutations in numerous genes, including MYC-associated factor X (MAX). To establish whether PPGL phenotypic differences reflect a MAX-mediated mechanism and opposing influences of HIF2α and HIF1α, we combined observational investigations in PPGLs and gene-manipulation studies in two pheochromocytoma cell lines. In cell lines lacking Max, re-expression of the gene resulted in maturation of phenotypic features and decreased cell cycle progression. In cell lines lacking Hif2α, overexpression of the gene led to immature phenotypic features, failure of dexamethasone to induce differentiation and increased proliferation. HIF1α has opposing actions to HIF2α. These model systems explain the features observed in PPGLs due to mutations of MAX and other PPGL susceptibility genes.
2014-09-18 | GSE50941 | GEO
Project description:Opposing Effects of HIF1α and HIF2α on Chromaffin Cell Phenotypic Features and Tumor Cell Proliferation: Insights from MAX [human]
| PRJNA221143 | ENA
Project description:Pheochromocytomas and paragangliomas (PPGLs) are catecholamine-producing tumors with diverse phenotypic features reflecting mutations in numerous genes, including MYC-associated factor X (MAX). To establish whether PPGL phenotypic differences reflect a MAX-mediated mechanism and opposing influences of HIF2M-NM-1 and HIF1M-NM-1, we combined observational investigations in PPGLs and gene-manipulation studies in two pheochromocytoma cell lines. In cell lines lacking Max, re-expression of the gene resulted in maturation of phenotypic features and decreased cell cycle progression. In cell lines lacking Hif2M-NM-1, overexpression of the gene led to immature phenotypic features, failure of dexamethasone to induce differentiation and increased proliferation. HIF1M-NM-1 has opposing actions to HIF2M-NM-1. These model systems explain the features observed in PPGLs due to mutations of MAX and other PPGL susceptibility genes. 88 samples (primary pheochromocytoma (PCC)/paraganglioma tumors) were hybridized onto a cDNA microarray in order to investigate possible heterogeneity within these tumors. This series of tumors is an expansion of GSE19422 that includes nine additional tumors to examine the role of MAX mutations in PCC/PGL.
2014-09-18 | E-GEOD-51081 | biostudies-arrayexpress
Project description:Hyperbaric oxygen enhances glioma chemosensitivity, but the mechanism remains unclear. Hypoxia is common in gliomas, and as the main effector molecules of hypoxia, HIF1α and HIF2α promote the malignant progression by inhibiting cell apoptosis and maintaining stemness. ABCG2 is a marker protein of tumor stem cells and drug efflux transporter protein. This study aims to reveal the detailed mechanism of hyperbaric oxygen promote both proliferation and chemosensitization. Under hyperbaric oxygen and hypoxic conditions, we investigated the differences in cell cycle, proliferation, apoptosis, LDH release, and the expression of proteins and mRNA. We also conducted studies on transcriptional regulation and performed in vivo experiments. It revealed that under hypoxic conditions, HIF1α, HIF2α, and ABCG2 are highly expressed, and both HIF1α and HIF2α promote ABCG2 expression. After hyperbaric oxygen treatment, the expression of HIF1α, HIF2α, and ABCG2 decreased, both cell proliferation and chemosensitivity increased. After knocking out HIF1α and HIF2α, cell proliferation and chemosensitivity increased, but the expression of stem cell marker proteins decreased. ChIP‒qPCR revealed that HIF1α and HIF2α target the ABCG2 promoter. Gain- and loss-of-function experiments suggested that ABCG2 can promote the expression of stem cell marker proteins, inhibit cell apoptosis, and promote tumor progression. This study confirmed that hyperbaric oxygen can inhibit ABCG2 expression through HIF1α and HIF2α, thereby promoting the proliferation and chemosensitization of gliomas.
2025-04-30 | GSE295278 | GEO
Project description:Clear cell renal cell carcinoma (ccRCC), the most common type of renal cancer is often associated with inactivation of the tumor suppressor gene von-Hippel Lindau (VHL), leading to stable expression of hypoxia inducible factors, HIF1α and HIF2α. Although HIF1α functions as a tumor suppressor gene, majority of ccRCCs constitutively express HIF1α, stratifying VHL-deficient ccRCCs into groups which express either both HIF1α and HIF2α (H1H2) or HIF2α exclusively (H2). MicroRNA (miRNA) profiling performed in these two ccRCC subtypes to identify novel molecular mechanisms. ccRCCs were classified into H1H2 and H2 subtypes by immunohostochemical staining of H1F1α and H1F2α expression. Five H1H2 tumor samples and eight H2 tumor samples were used for the study. Matched adjacent normal renal tissues were used as respective controls.
2013-09-30 | E-GEOD-47582 | biostudies-arrayexpress
Project description:HIF1α promotes glioblastoma cell proliferation and tumorigenesis under hypoxia conditions, leading to poor prognosis; however, none of the targeted therapies of HIF1α for glioblastoma is success nowadays. Therefore, we focused to look for the reason and wondered whether HIF2α contributed GBM growth. We did gene-chip and found that HIF2α contributed to the malignant progression of glioblastoma while blocking of HIF1α. Furthermore, our results revealed knock-out of HIF1α and HIF2α simultaneously improved the chemo-sensitization significantly. Moreover, miR-210-3p induced HIF1α expression but inhibited HIF2α, which meant the existence of regulation of cycle between HIF1α/HIF2α and miR-210-3p. Traditional studies have proved EGF as an upstream gene regulator of HIF1α in hypoxia conditions through EGFR-PI3K/AKT-mTOR signaling pathway. However, in this study, besides the signaling pathways mentioned above, we found the upstream regulators HIF1α and HIF2α also promoted EGF with the binding regions AGGCGTGG and GGGCGTGG. Briefly, in hypoxia microenvironment HIF1α/HIF2α-miR210-3p network promotes malignant progression of glioblastoma through EGFR-PI3K/AKT-mTOR signaling pathway with a positive feedback.
2020-11-24 | GSE142719 | GEO
Project description:Clear cell renal cell carcinoma (ccRCC), the most common type of renal cancer is often associated with inactivation of the tumor suppressor gene von-Hippel Lindau (VHL), leading to stable expression of hypoxia inducible factors, HIF1α and HIF2α. Although HIF1α functions as a tumor suppressor gene, majority of ccRCCs constitutively express HIF1α, stratifying VHL-deficient ccRCCs into groups which express either both HIF1α and HIF2α (H1H2) or HIF2α exclusively (H2). MicroRNA (miRNA) profiling performed in these two ccRCC subtypes to identify novel molecular mechanisms.
2013-09-30 | GSE47582 | GEO