Molecular mechanisms of functional adrenocortical adenoma and carcinoma: Genetic characterization and intracellular signaling pathway

Hiroki Shimada, Yuto Yamazaki, Akira Sugawara, Hironobu Sasano, Yasuhiro Nakamura

Research output: Contribution to journalReview articlepeer-review

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Article number892
JournalBiomedicines
Volume9
Issue number8
DOIs
Publication statusPublished - 2021 Aug

Keywords

  • Adrenocorti-cal carcinoma (ACC)
  • Aldosterone-producing adenoma (APA)
  • Cortisol-producing adenoma (CPA)
  • Gene mutation
  • Transcription factors

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)

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