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Link between steroidogenesis, the cell cycle, and PKA in adrenocortical tumor cells

Abstract : Adrenocortical tumors (ACTs) frequently cause steroid excess and present cell-cycle dysregulation. cAMP/PKA signaling is involved in steroid synthesis and play a role in cell-cycle regulation. We investigated, by cell synchronization in the different phases of the cell-cycle, the control of steroidogenesis and the contribution of PKA in adrenocortical cells (H295R and culture of primary pigmented nodular adrenocortical disease cells). Cells showed increased steroidogenesis and a maximal PKA activity at G2 phase, and a reduction at G1 phase. PRKACA overexpression, or cAMP stimulation, enhanced PKA activity and induced steroidogenesis in all synchronized groups but is not sufficient to drive cell-cycle progression. PRKAR1A inactivation enhanced PKA activity and induced STAR gene expression, only in cells in G1, and triggered cell-cycle progression in all groups. These findings provide evidence for a tight association between steroidogenesis and cell-cycle in ACTs. Moreover, PRKAR1A is essential for mediating the function of PKA activity on both steroidogenesis and cell-cycle progression in adrenocortical cells.
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https://hal-cnrs.archives-ouvertes.fr/hal-03014038
Contributor : Marthe Rizk-Rabin <>
Submitted on : Thursday, November 19, 2020 - 11:37:35 AM
Last modification on : Friday, November 27, 2020 - 4:17:00 PM

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Marthe Rizk-Rabin, Sabrina Chaoui-Ibadioune, Anna Vaczlavik, Christopher Ribes, Michel Polak, et al.. Link between steroidogenesis, the cell cycle, and PKA in adrenocortical tumor cells. Molecular and Cellular Endocrinology, Elsevier, 2020, 500, ⟨10.1016/j.mce.2019.110636⟩. ⟨hal-03014038⟩

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