Proliferation-related expression of p19/nm23 nucleoside diphosphate kinase.
High level expression of the nm23-H1 gene, which encodes for a nucleoside diphosphate kinase, has been found to correlate with diminished metastasis in some tumors but not in others. We have previously identified the protein product of the nm23-H1 gene in two-dimensional electrophoretic gels and have designated it p19/nm23. In neuroblastoma, higher levels of p19/nm23, which are associated with amplification of the N-myc oncogene, large tumor mass, and metastasis, were observed in advanced stage tumors compared with limited stage disease. Because of the variable expression of nm23-H1 in different tumors, we have investigated the relationship between amounts of the protein and cell proliferation. The levels of p19/nm23 were compared between resting and mitotically stimulated normal human PBLs and in leukemia cells. The amount of p19/nm23 increased in normal lymphocytes in response to mitotic stimulation and paralleled the increase in DNA synthesis. In leukemia cells obtained from patients with different subtypes of acute leukemia, p19/nm23 levels were also increased relative to resting normal lymphocytes. Treatment of mitotically stimulated lymphocytes with cyclosporin, which inhibits proliferation, blocked the increase in p19/nm23; treatment of the leukemia cell line HL-60 with dimethylsulfoxide, which induces terminal differentiation, resulted in diminished levels of p19/nm23. Our data therefore provide evidence that nm23-H1 expression is related to cell proliferative activity.
Keim
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D
University of Michigan Medical School, Department of Pediatric Hematology, Ann Arbor 48109.
Hailat
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N
Melhem
R
R
Zhu
X X
XX
Lascu
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I
Veron
M
M
Strahler
J
J
Hanash
S M
SM
D005434:Flow Cytometry; D006801:Humans; D007938:Leukemia / Q000201:enzymology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000201:enzymology*; D009362:Neoplasm Metastasis; D009701:Nucleoside-Diphosphate Kinase / Q000032:analysis* / Q000276:immunology / Q000378:metabolism; D010766:Phosphorylation
D009701:Nucleoside-Diphosphate Kinase