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Cancer Chemotherapy and Pharmacology

, Volume 27, Issue 3, pp 171–177 | Cite as

Differential effect of 6-ethylmercaptopurine on c-myc expression in wild-type and HGPRT-deficient HL-60 cells

  • Bernard T. French
  • Dawn E. Patrick
  • Michael R. Grever
  • Ronald W. Trewyn
Original Articles Cell Differentiation, HL-60 Cells, Purine Analogs, C-Myc Expression
  • 27 Downloads

Summary

A variety of compounds inhibit the growth and induce differentiation of human promyelocytic leukemia (HL-60) cells. HL-60 subclones that lack the purine salvage enzyme hypoxanthine-guanine phosphoribosyl-transferase (HGPRT) can also be induced to differentiate with purine analogs. Mechanisms by which purine analogs induce differentiation offer unique possibilities for cancer chemotherapy. We have studied the effect of the purine analog 6-ethylmercaptopurine (e6MP) on the growth and induction of differentiation in both wild-type and HGPRT-deficient HL-60 cells. We have previously shown that e6MP inhibits cell growth in both wild-type and HGPRT-deficient HL-60 cells without activation through salvage pathways [8]. In this report we evaluate the effect of e6MP on c-myc mRNA expression. c-Myc mRNA, which is amplified in HL-60 cells, has been shown to play a role in the induction of granulocytic differentiation in HL-60 cells. e6MP transiently down-regulates c-myc mRNA in wild-type cells but has no efect on c-myc mRNA expression in HGPRT-deficient HL-60 cells. Despite the differential effects of e6MP on c-myc mRNA, both wild-type and HGPRT-deficient HL-60 cells appear to engage in terminal differentiation. The morphological changes and nonspecific esterase activity induced by e6MP suggest differentiation down the monocytic pathway. However, early monocytic markers such as the rapid induction of c-fos and the stabilization of c-fms mRNA are not observed. In addition, e6MP inhibits TPA-induced monocytic/macrophage differentiation as characterized by stabilization of c-fms mRNA and cellular adherence.

Keywords

Inhibit Cell Growth Esterase Activity Promyelocytic Leukemia Rapid Induction Salvage Pathway 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

e6MP

6-ethylmercaptopurine

6-TG

6-thioguanine

MP

6-mercaptopurine

8-AzaG

8-azaguanine

FBS

fetal bovine serum

HGPRT

hypoxanthine-guanine phosphoribosyltransferase

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Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • Bernard T. French
    • 1
  • Dawn E. Patrick
    • 1
  • Michael R. Grever
    • 1
  • Ronald W. Trewyn
    • 1
  1. 1.Comprehensive Cancer Center and Department of Physiological ChemistryThe Ohio State UniversityColumbusUSA

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