PROLIFERATION-RELATED EXPRESSION OF P19/NM23 NUCLEOSIDE DIPHOSPHATE KINASE
PROLIFERATION-RELATED EXPRESSION OF P19/NM23 NUCLEOSIDE DIPHOSPHATE KINASE
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DOI：
10.1172/jci115672
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发表时间：
1992-03-01
影响因子：
15.9
通讯作者：
HANASH, SM
中科院分区：
文献类型：
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作者：
KEIM, D;HAILAT, N;HANASH, SM
编码核苷二磷酸激酶的nm 23-H1基因的高水平表达已被发现与某些肿瘤的转移减少相关，但在其他肿瘤中则不相关。我们以前已经确定了蛋白质产品的nm 23-H1基因在二维电泳凝胶，并已指定为p19/nm 23。在神经母细胞瘤中，与局限期疾病相比，在晚期肿瘤中观察到更高水平的p19/nm 23，其与N-myc癌基因扩增、大肿瘤块和转移相关。由于nm 23-H1在不同肿瘤中的可变表达，我们研究了该蛋白的量与细胞增殖之间的关系。p19/nm 23的水平进行了比较之间的休息和有丝分裂刺激正常人PBLs和白血病细胞。p19/nm 23的量在正常淋巴细胞中响应于有丝分裂刺激而增加，并抑制DNA合成的增加。在从不同亚型急性白血病患者获得的白血病细胞中，p19/nm 23水平相对于静息正常淋巴细胞也增加。用抑制增殖的环孢菌素处理有丝分裂刺激的淋巴细胞，阻断了p19/nm 23的增加;用诱导终末分化的二甲亚砜处理白血病细胞系HL-60，导致p19/nm 23水平降低。因此，我们的数据提供的证据表明，nm 23-H1的表达与细胞增殖活性。
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.