HL-60세포의 분화에 따른 c-myc, c-Ha-ras, c-rafl 및 c-mos 암유전자의 발현

Abstract

The acute myelogeous leukemia cell line, HL-60 is capable of differentiating to granulocytes or monocytes, it provides a good model to understand gene expressions that are associated with cell differentiation. The present study has been investigated the effects of dimethyl sulfoxide(DMSO) and phorbol 12-myristate 13-acetate(TPA) on HL-60 cell differentiation and expressions of pr otooncogenes (c-myc. c-Ha-ras, c-rafl, and c-mos). DMSO(1.25%) and TP A (32 nM) induced HL-60 cells to more differentiated phenotypes as determined by various analytic methods. These inductions of differentiation were associated with a loss of proliferative capacity and decreases in clonogenic survival. To determine if modulations of these oncogenes were important in the differentiation of HL-60 cells to either granulocytes or monocytes, levels of mRNAs of these oncogenes were determined by Northen blot analysis at various times following treatment with DMSO and TPA. DMSO induced granulocytic differentiation of HL-60 cells and resluted in a down-regulation of c-myc expression and a transient up-regulation of c-Ha-ras expression. TPA induced monocytic differentiation of HL-60 cells and resulted in also a rapid decline of c-myc expression, while no detactable change in the level of c-Ha-ras mRNA was found. But there were not found detectable mRNA levels of c-rafl and c-mos in control group and DMSO- and TPA-treated group. These results suggest that changes in c-myc expression can be associated with the monocytic and gralulocytic differentiation of Hl-60 cells and the transient elevation of c-Ha-ras mRNA in HL-60 cells may correlated temporally with differentiation to granulocyte-lineage cells. These results also suggest that expression of c-rafl and c-mos may not be play a role in differentiation of HL-60 cells but further evaluations will be needed.