Heide I, Thiede C, Poppe K, de Kant E, Huhn D, Rochlitz C
Abteilung für Hämatologie und Onkologie, Universitätsklinikum Rudolf Virchow, Freien Universität Berlin, Germany.
Br J Cancer. 1994 Dec;70(6):1267-71. doi: 10.1038/bjc.1994.485.
It has been proposed that nm23-H1, a candidate suppressor gene for metastasis, plays an important role in metastasis formation of human tumours. In order to investigate its role in the progression of colorectal cancer, we analysed 22 liver metastases of this malignancy with respect to mutational changes, loss of heterozygosity and expression levels of nm23-H1. Although genetic alterations in nm23-H1 have recently been described in those colorectal adenocarcinomas which give rise to distant metastases, we were unable to detect any mutation in the coding sequence of nm23-H1 in the metastatic tissue itself. We further analysed the metastases with respect to allelic deletions at the chromosomal locus of nm23. However, no loss of heterozygosity could be detected in ten informative cases. Moreover, the mRNA expression levels of nm23-H1 in the metastatic tissues were not significantly different from those in normal colon mucosa. Thus, although nm23-H1 might be involved in metastasis suppression of certain tumour types, in colorectal tumour progression its role remains to be determined.
有人提出,nm23-H1作为一种转移候选抑制基因,在人类肿瘤转移形成中发挥重要作用。为了研究其在结直肠癌进展中的作用,我们分析了22例这种恶性肿瘤的肝转移灶,检测了nm23-H1的突变变化、杂合性缺失及表达水平。尽管最近在那些发生远处转移的结直肠腺癌中已报道了nm23-H1的基因改变,但我们在转移组织本身的nm23-H1编码序列中未检测到任何突变。我们进一步分析了转移灶中nm23染色体位点的等位基因缺失情况。然而,在10例信息充分的病例中未检测到杂合性缺失。此外,转移组织中nm23-H1的mRNA表达水平与正常结肠黏膜中的表达水平无显著差异。因此,尽管nm23-H1可能参与某些肿瘤类型的转移抑制,但在结直肠癌进展中其作用仍有待确定。