Changes in the expression of oncogenes encoding nuclear phosphoproteins but not c-Ha-ras have a relationship to monocytic differentiation of HL 60 cells.
HL 60 cells were subcloned into variants with different sensitivities to the differentiation-inducing effect of 1,25 dihydroxyvitamin D3 (1,25(OH)2D3), as shown by increased oxidative and phagocytic activity and the appearance of cytoplasmic alpha-naphthyl butyrate esterase. Brief treatment (4 h) with 1,25(OH)2D3 or 5-azacytidine (5-Aza CR) of sensitive sublines induced monocytic differentiation in a fraction of treated cells. The phenotypic differentiation induced by 1,25(OH)2D3 was preceded by altered expression of oncogenes c-myc and c-fos, but not of c-Ha-ras or of the constitutively expressed p72 gene. Treatment with 5-Aza CR had similar effects but in addition increased the rate of transcription of the c-Ha-ras oncogene. In partially resistant sublines exposure to 1,25(OH)2D3 or 5-Aza CR resulted in changes in the levels of c-myc and c-fos mRNA, but the expression of c-Ha-ras gene did not correlate with the phenotypic differentiation. When induction of differentiation in responsive cells was delayed by cycloheximide, a temporal correlation could be made between changes in the expression of the c-myc gene and differentiation. These results suggest that a reduction of the elevated levels of c-myc gene transcription in HL 60 cells is required for the initiation of monocytic differentiation, that the induction of c-fos gene expression is an early step in this process, and that the transient increase in the expression of c-Ha-ras gene by 5-Aza CR is not related to differentiation.
D002117:Calcitriol / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002999:Clone Cells / Q000166:cytology / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D009000:Monocytes / Q000166:cytology* / Q000378:metabolism; D009698:Nucleoproteins / Q000235:genetics*; D009857:Oncogenes / Q000187:drug effects; D010750:Phosphoproteins / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
D009698:Nucleoproteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D003513:Cycloheximide; D002117:Calcitriol