Searchable abstracts of presentations at key conferences in endocrinology

ea0049gp13 | Adrenal 2 | ECE2017

PRKARIA (Carney complex gene) is a major regulator of the tight link between cell cycle phases and steroidogenesis in the adrenocortical tumor cells H295R

Rizk-Rabin Marthe , Ragazzon Bruno , Bertherat Jerome

The cyclic AMP/PKA signalling cascade is involved in the pathogenesis of cortisol-secreting adrenocortical tumors (ACT). Defects in cell cycle checkpoints play a major role in oncogenesis. The PKA regulatory subunits PRKARIA and PRKARIIb are involved in cell survival and steroidogenesis in the adrenocortical carcinoma H295R cell line. We have previously shown that their inactivation enhances the accumulation of cells in the G2 phase and act...

ea0041oc2.4 | Receptors & Signalling | ECE2016

Link between cell cycle, steroidogenesis and PKA in adrenocortical tumors cells

Rizk-Rabin Marthe , Ragazzon Bruno , Bertherat Jerome

The cyclic AMP/PKA signalling cascade and PKA subunits are involved in the pathogenesis of a subset of cortisol-secreting adrenocortical tumors (ACT). In addition, steroid excess causes morbidity of all types of ACT.The PKA regulatory subunits PRKARIA, PRKARIIb control proliferation/apoptosis in the H295R adrenocortical cell line. Their inactivation enhances the accumulation of cells in the G2 phase, increases steroidogenesis and activa...

ea0022p37 | Adrenal | ECE2010

Inactivation of PRKARIA or PRKAR2B increases cell proliferation and decreases apoptosis, delineating distinct molecular mechanisms in adrenocortical human H295R cell line

Ragazzon Bruno , Bertherat Jerome , Rizk-Rabin Marthe

The cAMP signaling cascade is one of the main pathways involved in the pathogenesis of adrenocortical tumors (ACT). Protein kinase A (PKA) is a key element of this pathway. The R1A and R2B proteins are the most abundant regulatory subunits in endocrine tissues. Inactivating mutations of PRKAR1A are observed in Carney complex and a subset of ACT. We have recently reported that inactivation of PRKAR1A dysregulates cAMP pathway and reduces TGFβ-induced apoptosi...

ea0063gp13 | Adrenal and Neuroendocrine - Tumour | ECE2019

KCTD20, a new gene in cortisol-secreting adrenocortical tumors related to inactivating mutations of the Carney Complex gene (PRKAR1A)

Briere Mathilde , Ragazzon Bruno , Yu Bo , Bouchekioua Abdelghani , Bertherat Jerome , Rizk-Rabin Marthe

Introduction: Adrenal Cushing due to bilateral multiple adrenal tumors known as Primary Pigmented Nodular Adrenocortical Disease (PPNAD) can be observed in the multiple neoplasia syndrome Carney Complex or as an isolated disease. In both situations germline inactivating mutations of PRKAR1A (regulatory subunit R1A of PKA) can be observed. The loss of PKA R1A results in an increased PKA activity. Comparison of the transcriptome of PPNAD and stably transfected H295R adr...

ea0032p3 | Adrenal cortex | ECE2013

Correlation between cell cycle, steroidogenesis and PKA RIA and RIIB subunits in adrenocortical tumors cells

Basso Francesco , Rezaei Neda , Ragazzon Bruno , Bertherat Jerome , Rizk-Rabin Marthe

The cyclic AMP (cAMP) signalling cascade is one of the main pathways involved in the pathogenesis of adrenocortical tumors (ACT). PRKARIA or PRKARIIb are involved in the proliferation/apoptosis in a subset of tumors.Majors alterations of genes involved in both cell proliferation and the cell cycle have been described by transcriptome and miRNome analysis in various types of adrenocortical tumors (ACC, ACA, AIMAH, and PPNAD). In addition...

ea0016oc4.1 | Bone and adrenal | ECE2008

Inactivation of the Carney complex (CNC) gene 1 (PKA regulatory subunit 1A, PRKAR1A) by interference RNA alters multiple signaling pathways and decreases apoptosis

Ragazzon Bruno , Cazabat Laure , Rizk-Rabin Marthe , Perlemoine Karine , Martinez Antoine , Bertherat Jerome

The cAMP signaling pathway plays an important role in cell proliferation and differentiation, and can be altered at multiple levels in endocrine tumors. Its central component is the protein kinase A (PKA). Inactivating mutations of PRKAR1A are observed in CNC (a dominant autosomal hereditary disease responsible for primary pigmented nodular adrenocortical disease, cardiac myxoma and lentiginosis). Most PRKAR1A mutations lead to mRNA unstability and protein degrad...

ea0016p656 | Signal transduction | ECE2008

Consequences of PRKAR1A (Carney complex gene) inactivation on cellular and subcellular PKA activity monitored by FRET-based reporters

Cazabat Laure , Ragazzon Bruno , Varin Audrey , Perlemoine Karine , Zhang Jin , Bertherat Jerome , Vandecasteele Gregoire

cAMP/PKA pathway activation is frequently involved in endocrine tumors with overactivity. The Carney complex (CNC) is an autosomal dominant multiple endocrine neoplasia syndrome which associates cardiac myxomas, spotty skin pigmentation and endocrine overactivity. Mutations in the PRKAR1A gene located at 17q22-24 and encoding for the R1A regulatory subunit of protein kinase A have been found in about 60% of CNC. These mutations are heterozygous germline mutations leading to ab...

ea0073pep1.6 | Presented ePosters 1: Adrenal and Cardiovascular Endocrinology | ECE2021

ARMC5 modifies cell redox state to regulate steroidogenesis and lipid metabolism in the adrenal cortex

Isadora Pontes Cavalcante , Rizk-Rabin Marthe , Perlemoine Karine , Ribes Christopher , Jerome Bertherat , Ragazzon Bruno

BackgroundARMC5 is a putative tumor suppressor gene that is frequently mutated in primary bilateral macronodular adrenal hyperplasia (PBMAH), a rare cause of Cushing’s syndrome. The function of ARMC5 is poorly known, aside the fact that it regulates cell apoptosis and adrenal steroidogenesis in by mechanisms still unknown. Tumor suppressor genes play an important role in oxidative stress.MethodsIn this s...

ea0093p1 | Guided Poster Tour 1: Adrenal and Neuroendocrine tumors | EYES2023

Proposition of an histopathological classification of bilateral macronodular adrenal disease (BMAD) and its correlation with ARMC5 and KDM1A mutations

Violon Florian , Bouys Lucas , Berthon Annabel , Bruno Ragazzon , Barrat Maxime , Terris Benoit , Bertherat Jerome , Sibony Mathilde

Introduction: Bilateral macronodular adrenal disease (BMAD, former PBMAH) is a rare cause of Cushing’s syndrome. The few morphologic descriptions of BMAD mention multinodular hyperplastic adrenal glands composed of clear spongiocytic cells and fewer compact eosinophilic cells without any morphologic variation. The discovery of ARMC5 and KDM1A mutations argues for genetic heterogeneity. The aim of this work was to describe the morphological and immunohist...

ea0081p13 | Adrenal and Cardiovascular Endocrinology | ECE2022

ARMC5 as a possible regulator of acetylation in the adrenal cortex in partnership with SIRT1

Berthon Annabel , Faucz Fabio , Feldman Benjamin , Drougat Ludivine , espiard Stephanie , Pontes Cavalcante Isadora , Ragazzon Bruno , Bertherat Jerome , Stratakis Constantine

ARMC5 is a tumor suppressor gene responsible for 20 to 40% of Primary Bilateral Macronodular Adrenal Hyperplasia (PBMAH) with a function that remains unclear. Based on pathway analysis from RNAseq results obtained on zebrafish models of transient Armc5 up- and down-regulation, we identified transcriptional alterations of several members of SIRT1 (sirtuin (silent mating type information regulation 2 homolog) 1) signaling in our models and hypothesized that ARM...