Glucocorticoid polarization of primary human macrophages
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE329681 | GEO | 2026/05/06
REPOSITORIES: GEO
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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:Adrenocortical carcinoma is a rare tumour with a poor prognosis. The currently available medical treatment options of adrenocortical cancer are limited. In the present study we examine the potential antitumoral effects of 9-cis-retinoic acid (9-cisRA) on the adrenocortical cancer cell line NCI-H295R.
2013-02-10 | GSE43090 | GEO
Project description:The mineralocorticoid hormone, aldosterone, is secreted by the adrenal zona glomerulosa (ZG) in response to high plasma K+ and hypovolemia and promotes renal Na+ reabsorption and K+ secretion. Hence, the regulation of aldosterone secretion is critical for the control of ion homeostasis and blood pressure. While the kinase pathways regulating aldosterone production are well studied, little is known about the involved phosphatases. Using the human adrenocortical carcinoma cell line NCI-H295R, we found that the mRNA expression of the aldosterone synthase increases significantly within 6 hours after K+ exposure. This increase was inhibited in a dose-dependent manner by the calcineurin inhibitors tacrolimus and cyclosporine A. Calcineurin (Cn) is a serine-threonine-specific, Ca2+ and CaM-activated protein phosphatase essential for lymphocyte, neuronal and cardiac function. The physiologic role of Cn in the ZG cells and the molecular pathways by which Cn regulates the K+-stimulated secretion of aldosterone are unknown. To answer these questions, we stimulated NCI-H295R cells with K+ with or without Tacrolimus and studied the phosphorylation pattern of cytoplasmic proteins by phospho-proteomics. We generated a map of the changes in the Ser/Thr phosphorylation in adrenocortical cells upon stimulation with K+ and identified Cn-regulated phosphoproteins.
2023-05-25 | PXD027856 | Pride
Project description:Adrenocortical carcinoma is a rare tumour with a poor prognosis. The currently available medical treatment options of adrenocortical cancer are limited. In the present study we examine the potential antitumoral effects of 9-cis-retinoic acid (9-cisRA) on the adrenocortical cancer cell line NCI-H295R. For the gene expression profiling, H295R cells were treated for 24h with 9cisRA at a final concentration of 2.5*10-5, 5*10-5 and 7.5*10-5 M and for the contol with the same amount of ethanol.
2013-02-10 | E-GEOD-43090 | biostudies-arrayexpress
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:Pediatric adrenocortical tumor (ACT) is a rare neoplasm with high heterogeneity, exhibiting an incidence 10 to 15 times higher in the south and southeast regions of Brazil when compared to the global incidence.In this context, our aim was to analyze the gene expression profile in the adrenocortical carcinoma cell line (NCI-H295R) after treatment with the compound rottlerin.
2024-02-18 | GSE255729 | 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:The human glucocorticoid receptor (GRα) is overexpressed at the molecular and protein level in malignant human adrenocortical cancers. A stable cell line model of GRα overexpression was established using the H295R human adrenocortical cancer cell line. The following results were obtained from gene expression profiling of H295R_GRα and H295R_Control (empty vector) cells following treatment with either a GRα agonist (dexamethasone), GRα antagonist (RU486) or vehicle (ethanol) control.
2015-01-10 | GSE64826 | GEO
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: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