Glucocorticoid sensitivity and receptors in cells of human myelogenous leukemia lines.
The effect of dexamethasone on the clonal proliferation of human acute myelogenous leukemia cells was studied using the two available human acute myelogenous leukemia lines KG-1 and HL-60. The cells were cloned in agar in the presence of colony-stimulating activity with and without dexamethasone. Colony formation by KG-1 cells was inhibited by dexamethasone at a concentration of 10(-7) M, and a 50% reduction occurred at 10(-5) M dexamethasone. Dexamethasone had no effect on HL-60 colony formation. Direct assessment of dexamethasone binding showed that both KG-1 and HL-60 cells had high-affinity glucocorticoid receptors with a mean 10,300 and 15,600 binding sites/cell with a Kd of 3.3 x 10(-9) M and 4.2 x 10(-9) M (r greater than or equal to -0.95), respectively. Binding competition studies confirmed the specificity of these glucocorticoid receptors. No correlation was noted between the number of glucocorticoid receptors and the in vitro inhibition of colony formation. A variety of other steroids was tested and found to have no effect on clonal proliferation of the leukemic cells.
D001667:Binding, Competitive; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003907:Dexamethasone / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007700:Kinetics; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D011987:Receptors, Steroid / Q000378:metabolism*; D013256:Steroids / Q000378:metabolism
D011965:Receptors, Glucocorticoid; D011987:Receptors, Steroid; D013256:Steroids; D003907:Dexamethasone