The role of NFATc4 on aldosterone production in NCI-H295R human adrenocortical cell line
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PROVIDER: PRJNA937244 | ENA |
REPOSITORIES: ENA
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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: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.
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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.
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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.
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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.
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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:H295R human adrenocortical cells treated with or without angiotensin II (100 nM) for 3 hr. Keywords = adrenal angiotensin aldosterone Keywords: parallel sample
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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:AngiotensinII (AngII) binds to the type I angiotensin receptor in the adrenal cortex to initiate a cascade of events leading to the production of aldosterone, a master regulator of blood pressure and volume. While the key signaling pathways, transcription factors, and steroidogenic enzymes necessary for adrenocortical production have been identified, surprisingly little is known about post-transcriptional regulation of this process. To investigate this question, we performed a high-resolution RNA-seq time course of the AngII stimulation response in a steroidogenic human cell line (H295R). We identified twelve temporally distinct groups of gene expression responses important for various steps of aldosterone production. AngII response kinetics for many of these mRNAs revealed a coordinated increase in both synthesis and decay. These findings were validated in primary human adrenocortical cells stimulated ex vivo with AngII or ACTH.
2021-06-01 | GSE163801 | GEO
Project description:Angiotensin II (Ang-II) regulates adrenal steroid production and gene transcription through several signaling pathways. Changes in gene transcription occur within minutes after Ang-II stimulation, causing an acute increase in aldosterone production and subsequent increase in the overall capacity to produce aldosterone. Our goal was to compare the Ang-II regulation of early gene expression and confirm the upregulation of selected genes using quantitative real-time RT-PCR (qPCR) across three species: human, bovine, and rat. Experiment Overall Design: Microarray analysis was performed using samples from control and Ang-II-(10 nM) treated (1 hour) cells from human adrenocortical tumor cell line H295-R, and primary adrenal glomerulosa cells from bovine and rat, applied respectively to human HG-133 + 2 , bovine, and rat 230-2 Affymetrix chips. qPCR was performed to confirm upregulation of selected genes using mRNA. Dye Swap was not used. Human samples (H295R) include 3 replicates of Basal (controls) and 3 repeats of Angiotensin II samples. Human H295R cells include also a group of cycloheximide (protein synthesis blocker) and angiontensin II + cycloheximide in order to check if the genes were direct targets of angiotensin II.
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