Cargando…
Molecular Mechanisms of Functional Adrenocortical Adenoma and Carcinoma: Genetic Characterization and Intracellular Signaling Pathway
The adrenal cortex produces steroid hormones as adrenocortical hormones in the body, secreting mineralocorticoids, glucocorticoids, and adrenal androgens, which are all considered essential for life. Adrenocortical tumors harbor divergent hormonal activity, frequently with steroid excess, and disrup...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8389593/ https://www.ncbi.nlm.nih.gov/pubmed/34440096 http://dx.doi.org/10.3390/biomedicines9080892 |
_version_ | 1783742894578860032 |
---|---|
author | Shimada, Hiroki Yamazaki, Yuto Sugawara, Akira Sasano, Hironobu Nakamura, Yasuhiro |
author_facet | Shimada, Hiroki Yamazaki, Yuto Sugawara, Akira Sasano, Hironobu Nakamura, Yasuhiro |
author_sort | Shimada, Hiroki |
collection | PubMed |
description | The adrenal cortex produces steroid hormones as adrenocortical hormones in the body, secreting mineralocorticoids, glucocorticoids, and adrenal androgens, which are all considered essential for life. Adrenocortical tumors harbor divergent hormonal activity, frequently with steroid excess, and disrupt homeostasis of the body. Aldosterone-producing adenomas (APAs) cause primary aldosteronism (PA), and cortisol-producing adenomas (CPAs) are the primary cause of Cushing’s syndrome. In addition, adrenocortical carcinoma (ACC) is a highly malignant cancer harboring poor prognosis. Various genetic abnormalities have been reported, which are associated with possible pathogenesis by the alteration of intracellular signaling and activation of transcription factors. In particular, somatic mutations in APAs have been detected in genes encoding membrane proteins, especially ion channels, resulting in hypersecretion of aldosterone due to activation of intracellular calcium signaling. In addition, somatic mutations have been detected in those encoding cAMP-PKA signaling-related factors, resulting in hypersecretion of cortisol due to its driven status in CPAs. In ACC, mutations in tumor suppressor genes and Wnt-β-catenin signaling-related factors have been implicated in its pathogenesis. In this article, we review recent findings on the genetic characteristics and regulation of intracellular signaling and transcription factors in individual tumors. |
format | Online Article Text |
id | pubmed-8389593 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-83895932021-08-27 Molecular Mechanisms of Functional Adrenocortical Adenoma and Carcinoma: Genetic Characterization and Intracellular Signaling Pathway Shimada, Hiroki Yamazaki, Yuto Sugawara, Akira Sasano, Hironobu Nakamura, Yasuhiro Biomedicines Review The adrenal cortex produces steroid hormones as adrenocortical hormones in the body, secreting mineralocorticoids, glucocorticoids, and adrenal androgens, which are all considered essential for life. Adrenocortical tumors harbor divergent hormonal activity, frequently with steroid excess, and disrupt homeostasis of the body. Aldosterone-producing adenomas (APAs) cause primary aldosteronism (PA), and cortisol-producing adenomas (CPAs) are the primary cause of Cushing’s syndrome. In addition, adrenocortical carcinoma (ACC) is a highly malignant cancer harboring poor prognosis. Various genetic abnormalities have been reported, which are associated with possible pathogenesis by the alteration of intracellular signaling and activation of transcription factors. In particular, somatic mutations in APAs have been detected in genes encoding membrane proteins, especially ion channels, resulting in hypersecretion of aldosterone due to activation of intracellular calcium signaling. In addition, somatic mutations have been detected in those encoding cAMP-PKA signaling-related factors, resulting in hypersecretion of cortisol due to its driven status in CPAs. In ACC, mutations in tumor suppressor genes and Wnt-β-catenin signaling-related factors have been implicated in its pathogenesis. In this article, we review recent findings on the genetic characteristics and regulation of intracellular signaling and transcription factors in individual tumors. MDPI 2021-07-26 /pmc/articles/PMC8389593/ /pubmed/34440096 http://dx.doi.org/10.3390/biomedicines9080892 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Shimada, Hiroki Yamazaki, Yuto Sugawara, Akira Sasano, Hironobu Nakamura, Yasuhiro Molecular Mechanisms of Functional Adrenocortical Adenoma and Carcinoma: Genetic Characterization and Intracellular Signaling Pathway |
title | Molecular Mechanisms of Functional Adrenocortical Adenoma and Carcinoma: Genetic Characterization and Intracellular Signaling Pathway |
title_full | Molecular Mechanisms of Functional Adrenocortical Adenoma and Carcinoma: Genetic Characterization and Intracellular Signaling Pathway |
title_fullStr | Molecular Mechanisms of Functional Adrenocortical Adenoma and Carcinoma: Genetic Characterization and Intracellular Signaling Pathway |
title_full_unstemmed | Molecular Mechanisms of Functional Adrenocortical Adenoma and Carcinoma: Genetic Characterization and Intracellular Signaling Pathway |
title_short | Molecular Mechanisms of Functional Adrenocortical Adenoma and Carcinoma: Genetic Characterization and Intracellular Signaling Pathway |
title_sort | molecular mechanisms of functional adrenocortical adenoma and carcinoma: genetic characterization and intracellular signaling pathway |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8389593/ https://www.ncbi.nlm.nih.gov/pubmed/34440096 http://dx.doi.org/10.3390/biomedicines9080892 |
work_keys_str_mv | AT shimadahiroki molecularmechanismsoffunctionaladrenocorticaladenomaandcarcinomageneticcharacterizationandintracellularsignalingpathway AT yamazakiyuto molecularmechanismsoffunctionaladrenocorticaladenomaandcarcinomageneticcharacterizationandintracellularsignalingpathway AT sugawaraakira molecularmechanismsoffunctionaladrenocorticaladenomaandcarcinomageneticcharacterizationandintracellularsignalingpathway AT sasanohironobu molecularmechanismsoffunctionaladrenocorticaladenomaandcarcinomageneticcharacterizationandintracellularsignalingpathway AT nakamurayasuhiro molecularmechanismsoffunctionaladrenocorticaladenomaandcarcinomageneticcharacterizationandintracellularsignalingpathway |