Proliferation-related expression of p19/nm23 nucleoside diphosphate kinase

• Published in: The Journal of clinical investigation Vol. 89; no. 3; pp. 919 - 924
• Main Authors: KEIM, D, HAILAT, N, MELHEM, R, ZHU, X. X, LASCU, I, VERON, M, STRAHLER, J, HANASH, S. M
• Format: Journal Article
• Language: English
• Published: Ann Arbor, MI American Society for Clinical Investigation 01-03-1992
• Subjects: Biological and medical sciences; cell proliferation; correlation; expression; Flow Cytometry; Hematologic and hematopoietic diseases; Humans; leukemia; Leukemia - enzymology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphocyte Activation; Lymphocytes - enzymology; man; Medical sciences; Neoplasm Metastasis; neuroblastoma; nucleoside diphosphate kinase; Nucleoside-Diphosphate Kinase - analysis; Nucleoside-Diphosphate Kinase - immunology; Nucleoside-Diphosphate Kinase - metabolism; Phosphorylation; Human; Cell proliferation; Cell culture; Gene; Enzyme; Exploration; Malignant hemopathy; Metastasis; Lymphocyte; Nucleoside diphosphate kinase
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/JCI115672

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.