The effect of differentiation inducers alone or in combination on the degree of cellular differentiation and the level of c-nyc expression was assessed in human promyelocytic leukemia cell line HL-60. And the method of signal transduction in the cell was investigated in the same celL 1) TPA (12-0-tetradecanoyl phorbol-13-acetate)-treated HL-60 cells showed the morphological differentiation, while either calcium ionophore A231S7-, trifluoperazine-, or diltiazem-treated cells didn't. Among the three combinations of TPA and other agents, the calcium ionophore and TPA combination revealed the greatest effect on the cellular differentiation. Compared with control, the proliferation of cells treated with the inducers was suppressed. 2) Cells treated with the inducers, fixed onto nitrocellulose filter, and assessed by the method of dot blot hybridization showed that the c-myc RNA level of TPA-treated cells decreased and that of calcium ionophore-treated cells increased, while cells treated with the combination of these two agents produced a significant reduction in that level. And the c-myc RNA level of trifluoperazine- treated cells increased noticeably. 3) Poly (A+) mRNA was extracted from cells treat.ed with the inducers for 24 hours. Northern blot analysis showed that the c-myc expression of TPA-treated cell decreased and that of cells treated with the combination of calciuni ionophore and TPA decreased more, while the c-myc expression of trifluoperazine-treated cells increased significantly.
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