Evidence that phosphatidylinositol 3-kinase and p70S6K protein are involved in differentiation of HL-60 cells induced by calcitriol.

1,25-dihydroxyvitamin D3 (calcitriol) is not only an antirachitic agent, but also a well known regulator of cell differentiation. HL-60 promyelocytic leukemia cells differentiate to monocytes upon treatment with calcitriol. We describe here, that PI3-K inhibitors are able to block the differentiation induced by calcitriol in HL-60 cells. Also the downstream effector of PI3-K, p70S6K ribosomal protein kinase seems to be involved in HL-60 cell differentiation. PKC alpha and PKC delta are activated and translocated to the nucleus upon exposure of cells to calcitriol. However in our experiments the inhibition of PKC did not result in an inhibition of calcitriol induced differentiation of HL-60 cells. On the contrary, the use of thapsigargin, caused the differentiation process to stop.