Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2017) 49 GP13 | DOI: 10.1530/endoabs.49.GP13

ECE2017 Guided Posters Adrenal 2 (10 abstracts)

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

Marthe Rizk-Rabin 1 , Bruno Ragazzon 1 & Jerôme Bertherat 1,


1INSERM U1016, CNRS UMR8104 Paris Descartes University, Paris, France; 2Center for Rare Adrenal Diseases, Department of Endocrinology, Hôpital Cochin, Paris, France.

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 activates PKA and MAPkinases pathways.

This study investigates the correlation between the cell cycle phases and the adrenal steroid secretion, as well as their control by PKA.

Methods: Using pharmacologic drugs, H295R cells were synchronized at specific cell cycle check point (G1 phase), (S phase) and (G2 phase). The cell cycle distribution (Cytometry), the expression of cyclins, PKA subunits, cell signalling pathways, StAR and steroidogenic enzymes were analysed. The effect of PKA activation either by the different PKA subunits, or cAMP, PKA inactivation by H89 and PKI along the cell cycle synchronization were studied.

Results: Cells synchronized at G2 phase increased the expression of the steroidogenic enzymes and steroid secretion. Arresting H295R in G1 phase decreased the steroidogenic enzymes expression and cortisol secretion. PKA subunits distribution and PKA activity modulation were cell cycle dependent. PKA activation by PRKARIA inactivation counteracted specifically the decrease of steroidogenesis in cells arrested in G1 phase: StAR/luc reporter gene activity and cell progression in G2 phase were stimulated. PRKARIIb inactivation and PRKACA overexpression or cAMP increased the StAR/luc reporter gene activity, independently of the cell cycle check point arrest. The H89 and PKI differentially reduced StAR/luc reporter gene activity, and both reversed the cell cycle in the G2 arrested cells.

Conclusion: Inactivation of the Carney complex gene stimulates steroidogensis in the low steroidogenic G1 phase arrested cells. This study shows a link between the cell cycle check points and the regulation of steroidogenesis, in which the PRKARIA subunit is a key regulator of both cell cycle and steroidogenesis.

Volume 49

19th European Congress of Endocrinology

Lisbon, Portugal
20 May 2017 - 23 May 2017

European Society of Endocrinology 

Browse other volumes

Article tools

My recent searches

No recent searches.