Endocrine Abstracts

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...

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...

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...

Various alterations of the cyclic AMP (cAMP) signalling cascade has been observed in adrenocortical tumors. Changes of the PKA regulatory subunits expression in tumors may positively or negatively regulate proliferation. 8CL-cAMP, a site selective cAMP analogue, induces growth inhibition in a variety of human cancer cell lines. The aim of the study was to determine if 8CL-cAMP acts on adrenocortical carcinoma H295R cell growth.We have determined the invo...

Introduction: Adrenocortical Carcinoma (ACC) is a rare and aggressive tumor with poor prognosis. Up to now, CTNNB1 (βcatenin) and TP53 mutations were the most frequent alterations identified in ACC. By a combination of genomic approaches, we have recently analyzed a cohort of 122 ACC (European Network for the Study of Adrenal Tumors, ENSAT). This work confirmed recurrent alterations in CTNNB1 and TP53 and revealed new genes not previous...

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...

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...

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...

Grb14 is a molecular adaptor that inhibits insulin signaling by interacting with the activated insulin receptor and inhibiting its tyrosine kinase activity. In various models of insulin resistance, including obese mice and type 2 diabetes patients, an inverse correlation was reported between Grb14 expression in adipose tissue and insulin sensitivity. To elucidate Grb14 function in this specific tissue, we studied the impact of modifications of Grb14 level of expression on adip...

Introduction: The inactivating mutations of the Carney complex gene PRKAR1A (regulatory subunit RIA of PKA) cause bilateral adrenocortical tumors (PPNAD: Primary Pigmented Nodular Adrenocorticel disease) over-secreting cortisol. This leads to stimulation of PKA activity, however the mechanisms of adrenal tumorigenesis and cortisol dysregulation are not fully understood. In order to identify target genes of PRKAR1A inactivation in adrenal cortex we undertook a comparat...