Acth inhibits a ras-dependent anti-apoptotic and mitogenic pathway in mouse Y1 adrenocortical cells

Mouse Y1 adrenocortical tumor cells harbor amplified and overexpressed cKi- ras gene, displaying relatively high constitutive levels of Ras GTP. Here w e report that Y1 cells also constitutively display high levels of phosphory lated AKT/PKB, that are dependent on Ras . GTP and PI3K. ACTH rapidly cause s dephosphorylation of AKT/PKB in a cAMP/PKA dependent maner. This ACTH inh ibition of the anti-apoptic and mitogenic AKT/PKB pathway is likely to be r elevant in ACTH growth inhibitory effects in Y-1 adrenocortical cells.