Constitutive activation of phosphatidylinositol 3-kinase (PI3K)/Akt signaling has been observed in up to 70% of acute myeloid leukemia. Class I(A) PI3K consists of a catalytic subunit (p110 , p110 , p110 ) and an adapter subunit (p85 , p55 , p50 , p85 , p55 ). The p85 adapter subunit stabilizes the catalytic p110 subunit and recruits p110 to the plasma membrane. In addition, p85 inhibits the basal activity of p110 and can negatively regulate signal transduction, as shown for insulin and GM-CSF receptor signaling. Here, we describe that the expression of p85 is posttranscriptionally regulated in several human and murine leukemia cell lines and in a Hodgkin lymphoma cell line (CO) by translational repression. A detailed analysis of CO cells revealed that both wild type and a mutated p85 mRNA are detectable at similar ratios in the nucleus and polysomes. However, while the mutated p85 protein is expressed in CO cells, translation of the wild type p85 mRNA is completely inhibited. Ectopic expression of wild type p85 from a retroviral vector is suppressed in CO cells and in five out of six leukemia cell lines. Our data indicate that leukemia cells can regulate the expression of p85 by posttranscriptional regulation.
