Evidence that phosphatidylinositol 3-kinase and p70(S6K) protein are involved in differentiation of HL-60 cells induced by calcitriol

1,25-dihydroxyvitamin D3 (calcitriol) is not only an antirachitic agent, bu t also a well known regulator of cell differentiation. HL-60 promyelocytic leukemia cells differentiate to monocytes upon treatment with calcitriol [1 , 2]. We describe here, that PI3-K inhibitors are able to block the differe ntiation induced by calcitriol in HL-60 cells. Also the downstream effector of PI3-K p70(S6K) ribosomal protein kinase [3] seems to be involved in HL- 60 cell differentiation. PKC alpha and PKC delta are activated and transloc ated to the nucleus upon exposure of cells to calcitriol [4]. However in ou r experiments the inhibition of PKC did not result in an inhibition of calc itriol induced differentiation of HL-60 cells. On the contrary, the use of thapsigargin, caused the differentiation process to stop.