Fujimoto Y, Ohtake T, Nishimori H, Ikuta K, Ohhira M, Ono M, Kohgo Y
Third Department of Internal Medicine, Asahikawa Medical College, Japan.
J Gastroenterol. 1998 Jun;33(3):368-75. doi: 10.1007/s005350050098.
We investigated the expression and genomic alteration of nm23-H1 (which encodes a nucleoside diphosphate, kinase A) in 12 human hepatocellular carcinomas (HCCs) and four hepatoma cell lines. The expression of nm23-H1 protein was significantly reduced in HCCs with intrahepatic metastasis (72%) compared with expression in HCCs without intrahepatic metastasis (38%). However, in two of three HCCs examined that had marked reduction of nm23-H1 protein, the nm23-H1 mRNA level was not reduced. A hepatoma cell line, HLF (phenotype, poorly differentiated carcinoma) revealed marked reduction of nm23-H1 protein compared with two other hepatoma cell lines, HuH-1 and HuH-2, although the mRNA level was similar in the three cell lines. No allelic deletion of the nm23-H1 gene was detected in the 12 HCCs examined. No point mutation in the coding region of the nm23-H1 gene was observed in any of the 12 HCCs or the four hepatoma cell lines. These findings suggest that: (i) the expression of nm23-H1 protein is inversely associated with high metastatic potential of HCC, (ii) regulation of nm23-H1 expression may occasionally occur at both the transcriptional and post-transcriptional levels in HCC; and (iii) genomic alteration of nm23-H1 is a rare event in HCC.
我们研究了12例人类肝细胞癌（HCC）和4种肝癌细胞系中nm23-H1（编码核苷二磷酸激酶A）的表达及基因改变情况。与无肝内转移的HCC（38%）相比，有肝内转移的HCC中nm23-H1蛋白表达显著降低（72%）。然而，在检测的3例nm23-H1蛋白明显降低的HCC中，有2例nm23-H1 mRNA水平并未降低。一种肝癌细胞系HLF（表型为低分化癌）与另外两种肝癌细胞系HuH-1和HuH-2相比，nm23-H1蛋白明显降低，尽管这三种细胞系的mRNA水平相似。在所检测的12例HCC中未检测到nm23-H1基因的等位基因缺失。在12例HCC或4种肝癌细胞系中，均未观察到nm23-H1基因编码区的点突变。这些发现提示：（i）nm23-H1蛋白的表达与HCC的高转移潜能呈负相关；（ii）HCC中nm23-H1表达的调控偶尔可能在转录和转录后水平同时发生；（iii）nm23-H1的基因改变在HCC中是罕见事件。
