Alterations in tyrosine phosphorylation during the granulocytic maturation of HL-60 leukemia cells.

Abstract

Granulocytic maturation of HL-60 promyelocytic leukemia cells induced by dimethylsulfoxide has been shown to produce a decrease in cellular protein phosphotyrosine residues and increases in both tyrosine kinase and protein phosphotyrosine phosphatase activities (D. A. Frank and A. C. Sartorelli, Biochem. Biophys. Res. Commun., 140: 440-447, 1986). These changes have been shown to not be restricted to dimethylsulfoxide-induced differentiation, since similar changes occur in HL-60 cells initiated with retinoic acid and in HL-60 sublines resistant to dimethylsulfoxide-induced differentiation treated with the retinoid. These regulatory events are not directly coupled to growth arrest, which accompanies terminal maturation, since the anthracycline antibiotics aclacinomycin A and marcellomycin, which induce HL-60 differentiation, cause these changes in phosphotyrosine metabolism, while Adriamycin, at a level which produces an equivalent degree of growth inhibition but does not initiate the maturation of HL-60 cells, does not. Furthermore, an HL-60 subline deficient in hypoxanthine-guanine phosphoribosyltransferase, which differentiates in the presence of 6-thioguanine, produced a decrease in phosphotyrosine residues and increases in tyrosine kinase and phosphotyrosine phosphatase activities in response to the purine antimetabolite, while the parental HL-60 line, in which 6-thioguanine inhibits cellular proliferation but does not induce maturation, does not exhibit these changes. Finally, similar alterations in phosphotyrosine regulation were exhibited during anthracycline-induced differentiation of the murine myelomonocytic leukemia cell line WEHI-3B D+, supporting the concept that the phenomena measured represent a general response to inducers of the granulocytic differentiation of leukemia cells.

• Authors: D A Frank, A C Sartorelli
• Journal: Cancer research (Cancer Res) Vol. 48 Issue 1 Pg. 52-8 (Jan 01 1988) ISSN: 0008-5472 [Print] United States
• PMID: 2825968 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Anthracyclines
• Antibiotics, Antineoplastic
• Naphthacenes
• marcellomycin
• Tyrosine
• Aclarubicin
• Protein-Tyrosine Kinases
• Phosphoprotein Phosphatases
• Protein Tyrosine Phosphatases
• Thioguanine
• Dimethyl Sulfoxide

Topics

• Aclarubicin
• Anthracyclines
• Antibiotics, Antineoplastic
• Cell Differentiation (drug effects)
• Dimethyl Sulfoxide (pharmacology)
• Humans
• Leukemia, Myeloid, Acute (metabolism, pathology)
• Naphthacenes (pharmacology)
• Phosphoprotein Phosphatases (analysis)
• Phosphorylation
• Protein Tyrosine Phosphatases
• Protein-Tyrosine Kinases (analysis)
• Thioguanine (pharmacology)
• Tumor Cells, Cultured (metabolism)
• Tyrosine (metabolism)