Aberrant G protein-receptor expression is associated with DNA methylation in aldosterone-producing adenoma

Itcho, Kiyotaka; Oki, Kenji; Kobuke, Kazuhiro; Yoshii, Yoko; Ohno, Haruya; Yoneda, Masayasu; Hattori, Noboru

doi:10.1016/j.mce.2017.08.019

Cited by 31 publications

(24 citation statements)

References 27 publications

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“…PTGDR1 methylation from cervical scraping is a promising marker of endometrial cancer and ovarian cancer [28]. PTGER1 shows a strong association with DNA methylation in non-functioning adrenocortical adenoma [29]. The expression of PTGER2 is often silenced in neuroblastoma cell lines by epigenetic mechanisms [30].…”

Section: Discussionmentioning

confidence: 99%

Prostanoid receptor genes confer poor prognosis in head and neck squamous cell carcinoma via epigenetic inactivation

et al. 2020

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Background: Chronic inflammation is a risk factor for head and neck squamous cell carcinoma (HNSCC) and other diseases. Prostanoid receptors are clearly involved in the development of many types of cancer. However, their role is not simple and is poorly understood in HNSCC. Methods: Methylation profiles of prostanoid receptor family genes were generated for tumour samples obtained from 274 patients with HNSCC, including 69 hypopharynx, 51 larynx, 79 oral cavity, and 75 oropharynx tumour samples, by quantitative methylation-specific PCR. Promoter methylation was then evaluated with respect to various clinical characteristics and patient survival. Results: The mean number of methylated genes per sample was 2.05 ± 2.59 (range 0 to 9). Promoters of PTGDR1,

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Section: Discussionmentioning

confidence: 99%

Prostanoid receptor genes confer poor prognosis in head and neck squamous cell carcinoma via epigenetic inactivation

et al. 2020

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“…In fact, some in vitro experiments have shown that adenoma cells are hypersensitive to 5-HT and 5-HT4 receptor agonists [88]. Hyper-responsiveness to 5-HT4 receptor ligands has been ascribed to overexpression of 5-HT4 receptors in APAs [52,[89][90][91][92]. Upregulation of HTR4, the gene encoding the 5-HT4 receptor, may be due to hypomethylation of its promoter region [92].…”

Section: Mast Cells In Pathophysiology Of Hyperaldosteronismmentioning

confidence: 99%

“…Hyper-responsiveness to 5-HT4 receptor ligands has been ascribed to overexpression of 5-HT4 receptors in APAs [52,[89][90][91][92]. Upregulation of HTR4, the gene encoding the 5-HT4 receptor, may be due to hypomethylation of its promoter region [92]. Hypersensitivity of tumor cells to 5-HT may also be explained by abnormal HTR4 mRNA splicing resulting in expression of 5-HT4 receptor isoforms different from those detected in normal adrenals [52].…”

Section: Mast Cells In Pathophysiology Of Hyperaldosteronismmentioning

confidence: 99%

Role of Mast Cells in the Control of Aldosterone Secretion

et al. 2020

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Mast cells are immune cells present in adrenals from various species. Proliferation and activation of adrenal mast cells seem to be influenced by environment, since they increase during summer and in response to sodium restriction in frogs and mouse, respectively. Although the physiological factors regulating adrenal mast cell activity have not been identified, they might involve neurotransmitters and the renin-angiotensin system. Some data indicate that adrenal mast cells stimulate proliferation of steroidogenic cells in the zona glomerulosa and activate the mineralocorticoid production. In human, mast cell degranulation stimulates aldosterone synthesis through the release of serotonin (5-HT) and activation of 5-HT4 receptors. Increase in mast cell population and upregulation of the 5-HT signaling pathway occur in aldosterone-producing adenomas. In particular, aldosterone-producing adenoma cells overexpress 5-HT4 receptors and are hyper-responsive to 5-HT4 receptor agonists. These data suggest that the intra-adrenal serotonergic regulatory system represents a potential target for development of both adrenal imaging methods to evaluate the lateralization of aldosterone production, and pharmacological treatments of primary aldosteronism.

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“…Finally, a recent methylome analysis revealed hypomethylation of CYP11B2 in APA and a higher demethylation of G protein-coupled receptors (GPCRs) and GPCR-related genes (Itcho et al 2018). Thus, this hypomethylation may stimulate aldosterone production in APA through receptors that would regulate gene transcription like ACTH, glucagon, somatostatin, parathyroid hormone and glutamate metabotropic receptors.…”

Section: Genomic and Proteomic Alterations In Apamentioning

confidence: 99%

Molecular mechanisms in primary aldosteronism

Sousa

Abdellatif

Zein

et al. 2019

Journal of Endocrinology

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Primary aldosteronism (PA) is the most common form and an under-diagnosed cause of secondary arterial hypertension, accounting for up to 10% of hypertensive cases and associated to increased cardiovascular risk. PA is caused by autonomous overproduction of aldosterone by the adrenal cortex. It is mainly caused by a unilateral aldosterone-producing adenoma (APA) or bilateral adrenal hyperplasia. Excess aldosterone leads to arterial hypertension with suppressed renin, frequently associated to hypokalemia. Mutations in genes coding for ion channels and ATPases have been identified in APA, explaining the pathophysiology of increased aldosterone production. Different inherited genetic abnormalities led to the distinction of four forms of familial hyperaldosteronism (type I to IV) and other genetic defects very likely remain to be identified. Somatic mutations are identified in APA, but also in aldosterone-producing cell clusters (APCCs) in normal adrenals, in image-negative unilateral hyperplasia, in transitional lesions and in APCC from adrenals with bilateral adrenal hyperplasia (BAH). Whether these structures are precursors of APA or whether somatic mutations occur in a proliferative adrenal cortex, is still a matter of debate. This review will summarize our knowledge on the molecular mechanisms responsible for PA and the recent discovery of new genes related to early-onset and familial forms of the disease. We will also address new issues concerning genomic and proteomic changes in adrenals with APA and discuss adrenal pathophysiology in relation to aldosterone-producing structures in the adrenal cortex.

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Aberrant G protein-receptor expression is associated with DNA methylation in aldosterone-producing adenoma

Cited by 31 publications

References 27 publications

Prostanoid receptor genes confer poor prognosis in head and neck squamous cell carcinoma via epigenetic inactivation

Prostanoid receptor genes confer poor prognosis in head and neck squamous cell carcinoma via epigenetic inactivation

Role of Mast Cells in the Control of Aldosterone Secretion

Molecular mechanisms in primary aldosteronism

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