Inhibition by 1,25 dihydroxyvitamin D3 of c-myc down-regulation and DNA fragmentation in cytosine arabinoside-induced erythroid differentiation of K562 cells.
The effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on DNA fragmentation, altered expression of the heat shock protein (hsp) 70 gene, and protooncogenes c-myc and c-myb was studied during chemical induction of erythroid differentiation in K562 cells. Preincubation of K562 cells with 1,25(OH)2D3 did not alter the concentration of hemoglobin in cells which did differentiate, but led to a reduction in the accumulation of low molecular weight DNA generated by Ara-C administration. The extent of this reduction was similar to the degree of inhibition of hemoglobin formation in the culture as the whole. Preincubation with 1,25(OH)2D3 had no effect on the increase of hsp 70 gene expression induced by a 48-hr treatment with Ara-C, but prevented the Ara-C-induced down-regulation of the protooncogene c-myc. The protooncogene c-myb was down-regulated after 15 min of treatment with Ara-C, and exposure to 1,25(OH)2D3 prior to Ara-C caused a further down-regulation of its expression. The data suggest that the events associated with erythroid differentiation may be separable into at least two groups; one of these may have an influence on the kinetics of the cell cycle traverse, and the other may be related to the expression of the erythroid phenotype.
Moore
D C
DC
Department of Laboratory Medicine and Pathology, UMD-New Jersey Medical School, Newark 07103.
Carter
D L
DL
Studzinski
G P
GP
D015152:Blotting, Northern; D002117:Calcitriol / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003561:Cytarabine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004247:DNA / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism; D016259:Genes, myc / Q000187:drug effects* / Q000235:genetics; D006360:Heat-Shock Proteins / Q000235:genetics; D006410:Hematopoiesis / Q000187:drug effects* / Q000235:genetics; D006454:Hemoglobins / Q000096:biosynthesis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D004915:Leukemia, Erythroblastic, Acute; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D020598:Proto-Oncogene Proteins c-myb; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D012333:RNA, Messenger / Q000235:genetics; D014407:Tumor Cells, Cultured
D006360:Heat-Shock Proteins; D006454:Hemoglobins; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D003561:Cytarabine; D004247:DNA; D002117:Calcitriol