Effects of 1-beta-D-arabinofuranosylcytosine on proto-oncogene expression in human U-937 cells

T Mitchell, E Sariban and D Kufe

We have previously demonstrated that declines in c-myc expression precede the induction of c-fos and c-fms transcripts during monocytic differentiation of human leukemia (HL-60 and U-937) cell lines. The present study has monitored the effects of 1-beta-D- arabinofuranosylcytosine (ara-C) on proto-oncogene expression in U-937 cells. The results demonstrate that ara-C inhibits both U-937 proliferation and c-myc expression in a concentration- and time- dependent manner. At non-toxic concentrations of ara-C, these decreases in c-myc RNA occur in the absence of changes in the level of actin transcripts. The results also demonstrate that ara-C increases c-fos but not c-fms expression. Similar findings have been obtained with retinoic acid. Furthermore, although both agents induce a more mature U- 937 phenotype, ara-C is a relatively weak inducer of these cells. These findings would suggest that the changes in proto-oncogene expression induced by ara-C may be related to induction of differentiation or the inhibitory effects of this agent on proliferation.

Volume 30, Issue 4, pp. 398-402, 10/01/1986
Copyright © 1986 by American Society for Pharmacology and Experimental Therapeutics

This article has been cited by other articles:

				M. Kaneki, S. Kharbanda, P. Pandey, K. Yoshida, M. Takekawa, J.-R. Liou, R. Stone, and D. Kufe Functional Role for Protein Kinase Cbeta as a Regulator of Stress-Activated Protein Kinase Activation and Monocytic Differentiation of Myeloid Leukemia Cells Mol. Cell. Biol., January 1, 1999; 19(1): 461 - 470. [Abstract] [Full Text] [PDF]