Brelvi Z S, Christakos S, Studzinski G P
Lab Invest. 1986 Sep;55(3):269-75.
Monocytic differentiation of cultured leukemic cells HL60 can be induced by a variety of compounds including analogs of vitamin D3. We studied the expression of oncogenes c-fos, c-fms, c-fes, c-myb, c-myc, and c-Ha-ras during this process, and attempted to relate these and a conventional marker of monocytic differentiation, the nonspecific esterase activity, to changes in cytosol levels of the Ca2+-binding proteins. The analogs of vitamin D3, 1 alpha,25-dihydroxycholecalciferol, 1 alpha,25-dihydroxy-26,27-hexafluorocholecalciferol, and 1 alpha,25-dihydroxy-24R-fluorocholecalciferol, reduced the total calcium binding activity and the cellular levels of calmodulin, but calbindin D28k could not be detected in HL 60 cells. A correlation was evident between the potency of these compounds as inducers of differentiation demonstrated by nonspecific esterase activity, the degree of reduction in calmodulin concentration, the rate of the inhibition of DNA synthesis and of expression of c-myc and c-myb genes, and the induction of the expression of oncogenes c-fos and c-fms. These experiments indicate that the events which underlie monocytic differentiation of HL 60 cells can be observed to occur in discrete steps which include an inhibition of DNA synthesis, a reduction of cellular levels of calmodulin, and altered expression of several oncogenes.
培养的白血病细胞HL60的单核细胞分化可由多种化合物诱导，包括维生素D3的类似物。我们研究了原癌基因c-fos、c-fms、c-fes、c-myb、c-myc和c-Ha-ras在此过程中的表达，并试图将这些基因以及单核细胞分化的传统标志物非特异性酯酶活性与Ca2+结合蛋白胞浆水平的变化联系起来。维生素D3的类似物，1α,25-二羟基胆钙化醇、1α,25-二羟基-26,27-六氟胆钙化醇和1α,25-二羟基-24R-氟胆钙化醇，降低了总钙结合活性和钙调蛋白的细胞水平，但在HL 60细胞中未检测到钙结合蛋白D28k。这些化合物作为分化诱导剂的效力，通过非特异性酯酶活性证明，与钙调蛋白浓度的降低程度、DNA合成抑制率、c-myc和c-myb基因的表达抑制率以及原癌基因c-fos和c-fms表达的诱导之间存在明显的相关性。这些实验表明，HL 60细胞单核细胞分化所依据的事件可以观察到以离散步骤发生，包括DNA合成的抑制、钙调蛋白细胞水平的降低以及几种原癌基因表达的改变。
