Differential expression of the protein kinase A subunits in normal adrenal glands and adrenocortical adenomas

Research output: Contribution to journalArticle

Authors

  • Isabel Weigand
  • Cristina L Ronchi
  • Marthe Rizk-Rabin
  • Guido Di Dalmazi
  • Vanessa Wild
  • Kerstin Bathon
  • Beatrice Rubin
  • Felix Beuschlein
  • Jérôme Bertherat
  • Martin Fassnacht
  • Silviu Sbiera

Colleges, School and Institutes

External organisations

  • Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Wuerzburg, Wuerzburg, Germany.
  • Department of Internal Medicine I (K.L., K.W., B.H., B.A., S.H.), University Hospital Würzburg, 97080 Würzburg, Germany; Clinical Endocrinology (M.Q.), Charité Campus Mitte, Charité University Medicine Berlin, 10117 Berlin, Germany; Medizinische Klinik und Poliklinik IV (A.S.D., M.R.), University Hospital Munich, 80336 Munich, Germany; Institute of Clinical Chemistry and Laboratory Medicine (H.W., A.H., N.F.), University Medicine Greifswald, 17489 Greifswald, Germany; Private Practice Endocrinology (H.W.), 99084 Erfurt, Germany; Department of Nephrology, Medical Faculty (L.C.R., I.Q.), Heinrich-Heine University Düesseldorf, 40225 Düsseldorf, Germany; and Department of Endocrinology and Metabolism (H.S.W.), Rostock University Medical Center, 18147 Rostock, Germany; Comprehensive Cancer Center Mainfranken & Department of Medicine I (C.T.F.), University of Wuerzburg, 97080 Wuerzburg, Germany.
  • Institut Cochin, INSERM U1016, CNRS UMR810, Department of Endocrinology, Reference Center for Rare Adrenal diseases, Assistance Publique Hôpiteaux de Paris, Hôpital Cochin, Descartes University, Paris, France.
  • Medizinische Klinik and Poliklinik IV, Ludwig-Maximilians University, Munich, Germany.
  • Institute of Pathology, University of Wuerzburg, Wuerzburg, Germany.
  • Institute of Pharmacology and Toxicology and Bioimaging Center, University of Wuerzburg, Wuerzburg, Germany.
  • Endocrinology Unit, Department of Medicine, University of Padua, Padua, Italy.
  • Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Wuerzburg, Wuerzburg, Germany. Sbiera_S@ukw.de.
  • Institute of Pharmacology and Toxicology and Bioimaging Center, University of Wuerzburg, Wuerzburg, Germany

Abstract

Somatic mutations in protein kinase A catalytic α subunit (PRKACA) were found to be causative for 30-40% of cortisol-producing adenomas (CPA) of the adrenal gland, rendering PKA signalling constitutively active. In its resting state, PKA is a stable and inactive heterotetramer, consisting of two catalytic and two regulatory subunits with the latter inhibiting PKA activity. The human genome encodes three different PKA catalytic subunits and four different regulatory subunits that are preferentially expressed in different organs. In normal adrenal glands all regulatory subunits are expressed, while CPA exhibit reduced protein levels of the regulatory subunit IIβ. In this study, we linked for the first time the loss of RIIβ protein levels to the PRKACA mutation status and found the down-regulation of RIIβ to arise post-transcriptionally. We further found the PKA subunit expression pattern of different tumours is also present in the zones of the normal adrenal cortex and demonstrate that the different PKA subunits have a differential expression pattern in each zone of the normal adrenal gland, indicating potential specific roles of these subunits in the regulation of different hormones secretion.

Details

Original languageEnglish
Article number49
JournalScientific Reports
Volume7
Publication statusPublished - 13 Mar 2017

Keywords

  • Immunohistochemistry, Kinases