Role of phospholipase A2 and prostaglandin E in growth and differentiation of myeloid leukemic cells.
Phospholipase A2 activity and prostaglandin E synthesis have been studied in different clones of myeloid leukemic cells, which differ in their competence to be induced to differentiate by the macrophage and granulocyte differentiation-inducing protein or the tumor promoter 12-O-tetradecanoyl phorbol-13-acetate (TPA). Clones that could be induced to differentiate by this protein showed a higher basal phospholipase A2 activity than clones that could not be induced to differentiate by this protein inducer. Cell competence to be induced to differentiate by TPA did not show this correlation, and the clone with the least ability to respond to TPA showed the lowest number of binding sites for [20-3H]phorbol 12,13-dibutyrate. Differentiation induced by the protein was accompanied by a 7-14-fold increase in prostaglandin E synthesis, whereas differentiation induced by TPA did not show this increase. Externally added prostaglandin E1 did not induce differentiation but inhibited cell proliferation and the degree of inhibition in the different clones was related to the basal phospholipase A2 activity. The results indicate that increase of prostaglandin E synthesis was not an essential pre-requisite for differentiation, that prostaglandin E seems to be involved in the inhibition of cell proliferation in association with phospholipase A2, and that the differentiation-inducing protein and TPA can induce differentiation by different pathways. The amount of basal phospholipase A2 activity was also related to previously found differences in the ability of the clones to develop desensitization to beta-adrenergic hormones or prostaglandin E1.
D000818:Animals; D002273:Carcinogens / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002999:Clone Cells; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D007700:Kinetics; D007942:Leukemia, Experimental / Q000503:physiopathology*; D007953:Leukemia, Radiation-Induced / Q000503:physiopathology; D051379:Mice; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000378:metabolism / Q000494:pharmacology; D010740:Phospholipases / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D011458:Prostaglandins E / Q000096:biosynthesis*
D002273:Carcinogens; D003115:Colony-Stimulating Factors; D010703:Phorbol Esters; D011458:Prostaglandins E; D015240:Phorbol 12,13-Dibutyrate; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2