Similar Datasets
Project description:Cholesterol deprivation drives DHEA biosynthesis in human adrenals
| PRJNA789937 | ENA
Project description:Androgens are essential for sexual development and reproduction. However, androgen regulation in health and disease is poorly understood. Previously, we showed that human adrenocortical H295R cells grown under starvation conditions acquire a hyperandrogenic steroid profile with changes in steroid metabolizing enzymes HSD3B2 and CYP17A1 essential for androgen production. Furthermore, we have shown that metformin inhibits androgen production of steroidogenic H295R cells and inhibits complex I activity of the respriatory chain. Therefore, to search for underlying mechanisms regulting androgen production and to understand the basic biology of androgens, we have characterized the gene expression profile of H295R cells grown under normal growth conditions, serum starvation (hyperandrogenic) growth conditions as well as after metformin treatment (hypoandrogenic). In this dataset, we first characterized the gene expression profile of H295R cells cultured under nromal growth vs serum-starved (hypernadrogenic) growth conditions. Expression profiling of starved H295R cells revealed alterations in genes involved in steroid and energy metabolism and signal transduction. We discovered two new gene networks around RARB and ANGPTL1, and show how they regulate androgen biosynthesis (Udhane SS et al.,2015). In a second part, we compared the gene expression profile of H295R cells grown under serum starvation (hyperandrogenic) conditions to metformin treated (hypoandrogenic) cells in search for the underlying androgen regulating network. (Udhane et al., manuscript in preparation).
2018-01-01 | GSE88795 | GEO
Project description:To investigate the role of NFATc4 in aldosterone production, we created NFATc4 knock-out NCI-H295R cell line and overexpressed active NFATc4 in wild type NCI-H295R cells. We then analyzed the transcriptome of the four cell types.
2023-05-12 | GSE225735 | GEO
Project description:We have recently identified a set of benzimidazolylurea derivatives including a representative compound (designated as CJ28), which inhibit both cortisol production and de novo cholesterol biosynthesis. To evaluate its putative mode-of-actions, we examined genome-wide RNA expression profiles of human adrenocortical carcinoma NCI-H295R cell cultures by treatment with CJ28 in comparison with metyrapone (MET), a well-established cortisol biosynthesis inhibitor.
2023-07-11 | GSE236435 | GEO
Project description:Purpose: ASA404 (Vadimezan) belongs to a class of agents with disrupting properties against tumor vasculature, which is partly mediated by TNFM-NM-1-signaling. Our aim was to investigate the potential therapeutic applicability of ASA404 against endocrine tumors. Experimental Design: We determined anti-tumoral effects in preclinical models of neuroendocrine tumors of the gastroenteropancreatic system [1] and adrenocortical cancer (NCI-H295R) by histology and immunohistochemistry. Furthermore, we characterized these models with their clearly different responsiveness regarding TNFM-NM-1 synthesis and signaling. Results: Upon treatment of tumor bearing mice significant anti-tumoral effects, an increase in TNFM-NM-1 as well as TNFM-NM-1-specific activation of downstream signaling were evident in the BON tumor model while no comparable effects were detectable for NCI-H295R. Two important modulator of TNFM-NM-1-signaling, toll-like-receptor 4 (TLR-4) and its adaptor protein LY96 were found highly expressed in BON tumors and transgenic expression in NCI-H295R partly restored TNFM-NM-1 responsiveness. Furthermore, expression of IRAK2-kinase, which has recently been linked to TLR-4-signaling as a mediator of sustained TNFM-NM-1 release was induced upon TNFM-NM-1-treatment in BON, but not in NCI-H295R cells. Finally, we identified TNFAIP3/A20, a member of an inhibitory feedback-loop downstream of both investigated signaling cascades, as overexpressed in the adrenocortical carcinoma tumor model. Subsequent analyses of clinical patient samples confirmed a correlation between tumor TNFAIP3 expression levels and overall survival in patients with ACC. Conclusions: Taken together our findings provide evidence that modulation of TNFM-NM-1-signaling could be of relevance both for the clinical course of ACC patients and as a marker of treatment response. BON or NCI-H295R tumor cells were treated in-vitro with TNFalpha and compared to unstimulated cells
2014-12-17 | E-GEOD-64250 | biostudies-arrayexpress
Project description:Transcription factor 21 (TCF21) directly binds and regulates SF1 in tumor and normal adrenocortical cells, and both are involved in the development and steroidogenesis of the adrenal cortex. TCF21 is a tumor suppressor gene and its expression is reduced in malignant tumors. In adrenocortical tumors, it is less expressed in adrenocortical carcinomas (ACC) than in adrenocortical adenomas (ACA) and normal tissue. However, a comprehensive analysis to identify TCF21 targets have not yet been conducted in any type of cancer. In this study, we performed Chromatin Immunoprecipitation and Sequencing (ChIP-Seq) in adrenocortical carcinoma cell line (NCI-H295R) overexpressing TCF21, with the aim of identifying TCF21 new targets. The five most frequently identified sequences corresponded to the PRDM7, CNTNAP2, CACNA1B, PTPRN2 and KCNE1B genes. Validation experiments showed that, in NCI-H295R cells, TCF21 regulates gene expression positively in PRDM7 and negatively in CACNA1B. Recently, it was observed that the N-type calcium channel v2.2 (Cav2.2) encoded by CACNA1B gene is important in Angiotensin II signal transduction for corticosteroid biosynthesis in NCI-H295R adrenocortical carcinoma cells. Indeed, TCF21 inhibits CACNA1B and Cav2.2 expression in NCI-H295R. In addition, in a cohort of 55 adult patients with adrenocortical tumor, CACNA1B expression was higher in ACC than ACA, and was related to poor disease-free survival in ACC patients. These results suggest a mechanism of steroidogenesis control by TCF21 in adrenocortical tumor cells, in addition to the control observed through SF1 inhibition. Importantly, steroid production could impair tumor immunogenicity, contributing to the immune resistance described in adrenal cancer.
2022-06-30 | GSE179308 | GEO
Project description:The human adrenocortical carcinoma cell line NCI-H295R treated with siRNA targeting SF-1 or RNF31 with luciferase-targeting siRNA as control. Combined with forskolin treatment.
2012-02-01 | E-MEXP-3259 | biostudies-arrayexpress
Project description:Purpose: ASA404 (Vadimezan) belongs to a class of agents with disrupting properties against tumor vasculature, which is partly mediated by TNFα-signaling. Our aim was to investigate the potential therapeutic applicability of ASA404 against endocrine tumors. Experimental Design: We determined anti-tumoral effects in preclinical models of neuroendocrine tumors of the gastroenteropancreatic system [1] and adrenocortical cancer (NCI-H295R) by histology and immunohistochemistry. Furthermore, we characterized these models with their clearly different responsiveness regarding TNFα synthesis and signaling. Results: Upon treatment of tumor bearing mice significant anti-tumoral effects, an increase in TNFα as well as TNFα-specific activation of downstream signaling were evident in the BON tumor model while no comparable effects were detectable for NCI-H295R. Two important modulator of TNFα-signaling, toll-like-receptor 4 (TLR-4) and its adaptor protein LY96 were found highly expressed in BON tumors and transgenic expression in NCI-H295R partly restored TNFα responsiveness. Furthermore, expression of IRAK2-kinase, which has recently been linked to TLR-4-signaling as a mediator of sustained TNFα release was induced upon TNFα-treatment in BON, but not in NCI-H295R cells. Finally, we identified TNFAIP3/A20, a member of an inhibitory feedback-loop downstream of both investigated signaling cascades, as overexpressed in the adrenocortical carcinoma tumor model. Subsequent analyses of clinical patient samples confirmed a correlation between tumor TNFAIP3 expression levels and overall survival in patients with ACC. Conclusions: Taken together our findings provide evidence that modulation of TNFα-signaling could be of relevance both for the clinical course of ACC patients and as a marker of treatment response.
2014-12-17 | GSE64250 | GEO
Project description:BackgroundTo identify the biochemical changes induced by sleep deprivation at a proteomic level, we compared the hippocampal proteome of rats either after 4 hours of sleep or sleep deprivation obtained by gentle handling. Because sleep deprivation might induce some stress, we also analyzed proteomic changes in rat adrenals in the same conditions. After sleep deprivation, proteins from both tissues were extracted and subjected to 2D-DIGE analysis followed by protein identification through mass spectrometry and database search.ResultsIn the hippocampus, 87 spots showed significant variation between sleep and sleep deprivation, with more proteins showing higher abundance in the latter case. Of these, 16 proteins were present in sufficient amount for a sequencing attempt and among the 12 identified proteins, inferred affected cellular functions include cell metabolism, energy pathways, transport and vesicle trafficking, cytoskeleton and protein processing. Although we did not observe classical, macroscopic effect of stress in sleep-deprived rats, 47 protein spots showed significant variation in adrenal tissue between sleep and sleep deprivation, with more proteins showing higher abundance following sleep. Of these, 16 proteins were also present in sufficient amount for a sequencing attempt and among the 13 identified proteins, the most relevant cellular function that was affected was cell metabolism.ConclusionAt a proteomic level, short term sleep deprivation is characterized by a higher expression of some proteins in the hippocampus and a lower abundance of other proteins in the adrenals (compared to normal sleep control). Altogether, this could indicate a general activation of a number of cellular mechanisms involved in the maintenance of wakefulness and in increased energy expenditure during sleep deprivation. These findings are relevant to suggested functions of sleep like energy repletion and the restoration of molecular stocks or a more global homeostasis of synaptic processes.
| S-EPMC2453108 | biostudies-literature
Project description:Gene expression profiles of human adrenocortical NCI-H295R cells treated with cortisol biosynthesis inhibitors
| PRJNA990799 | ENA