Gazzeri S, Brambilla E, Negoescu A, Thoraval D, Veron M, Moro D, Brambilla C
Groupe de recherche sur le cancer du poumon et des voies aériennes, Institut Albert Bonniot, La Tronche, France.
Lab Invest. 1996 Jan;74(1):158-67.
Levels of nm23-H1/nucleoside diphosphate/kinase A expression have been reported to correlate inversely with metastatic potential in some tumors but not in others. To clarify the role of nm23 in lung carcinoma, the genetic abnormalities of nucleoside diphosphate/kinase A/nm23-H1 were investigated at the DNA and protein levels. A series of 104 human lung tumors (42 neuroendocrine (NE) and 62 non-NE tumors) was analyzed for nm23-H1 protein expression by immunohistochemistry using one polyclonal and two monoclonal Ab and for genomic alterations using Southern blotting and single-strand conformation polymorphism. Overexpression of the nm23-H1 protein relative to the normal lung epithelia (pneumocyte and bronchial epithelial cells) was observed in 83% (35/42) of NE carcinomas and in 89% (55/62) of non-NE carcinomas. Eight of nine carcinoids exhibited an increased expression of nm23-H1 protein, suggesting that this overexpression of the nm23 protein is necessary for proliferation in any tumors. No significant correlation was found between nm23 staining and any clinicopathologic parameters in NE carcinoma or in adenocarcinoma. In squamous carcinoma, high levels of nm23-H1 protein expression were associated with tumor stage (p = 0.0036). Allelic deletion or genetic amplification was never found. No altered mobility was detected using single-strand conformation polymorphism analysis. These data show that nm23-H1 protein is overexpressed in a large number of lung tumors of all histologic types, in association with advanced tumor stage in squamous carcinoma. They also suggest that nm23-H1 might play a role in the progression of lung tumors rather than in antimetastatic function.
据报道，nm23-H1/核苷二磷酸/激酶A的表达水平在某些肿瘤中与转移潜能呈负相关，但在其他肿瘤中并非如此。为了阐明nm23在肺癌中的作用，我们在DNA和蛋白质水平上研究了核苷二磷酸/激酶A/nm23-H1的基因异常情况。我们使用一种多克隆抗体和两种单克隆抗体，通过免疫组织化学分析了104例人类肺肿瘤（42例神经内分泌（NE）肿瘤和62例非NE肿瘤）中nm23-H1蛋白的表达，并使用Southern印迹法和单链构象多态性分析了基因组改变情况。相对于正常肺上皮细胞（肺细胞和支气管上皮细胞），在83%（35/42）的NE癌和89%（55/62）的非NE癌中观察到nm23-H1蛋白的过表达。9例类癌中有8例表现出nm23-H1蛋白表达增加，这表明nm23蛋白的这种过表达对于任何肿瘤的增殖都是必要的。在NE癌或腺癌中，未发现nm23染色与任何临床病理参数之间存在显著相关性。在鳞状细胞癌中，高水平的nm23-H1蛋白表达与肿瘤分期相关（p = 0.0036）。从未发现等位基因缺失或基因扩增。使用单链构象多态性分析未检测到迁移率改变。这些数据表明，nm23-H1蛋白在所有组织学类型的大量肺肿瘤中过表达，与鳞状细胞癌的晚期肿瘤分期相关。它们还表明，nm23-H1可能在肺肿瘤的进展中起作用，而不是在抗转移功能中起作用。
