Haut M, Steeg P S, Willson J K, Markowitz S D
Ireland Cancer Center, Case Western Reserve University, Cleveland, OH.
J Natl Cancer Inst. 1991 May 15;83(10):712-6. doi: 10.1093/jnci/83.10.712.
Levels of expression of the murine nm23 gene inversely correlate with metastatic potential in several rodent tumor model systems. Expression of the human nm23 homologue also is lower in human breast cancers of high metastatic potential than in breast cancers of low metastatic potential. In the present study, we examined changes in nm23 expression during colon carcinogenesis as found in 18 matched pairs of normal and neoplastic human colon tissues. We found that a 0.8-kilo-base nm23 transcript was expressed in all samples of morphologically normal colon mucosa. In 16 of 18 colon neoplasms, nm23 expression was further increased in the neoplastic, compared with the morphologically normal, colon mucosa from the same individual. Expression of nm23 was elevated over normal mucosa in 3 of 3 polyps, in 2 of 3 nonmetastatic cancers, and in 11 of the 12 cancers that were metastatic at the initial presentation. The levels of nm23 expressed were similar in the 12 metastatic colon neoplasms and in the 6 colon neoplasms of lower clinical stage. In addition, nm23 expression was maintained in culture in each of 12 cell lines initiated from human colon neoplasms and did not differ between lines established from neoplasms of high or low metastatic capability. We concluded that nm23 was expressed in normal colon mucosa. Expression of nm23 increased during early stages of colon carcinogenesis and remained increased in metastatic colon cancer. Therefore, in the colon, tissue-specific events dissociate nm23 expression from loss of tumor metastatic competence.
在多个啮齿动物肿瘤模型系统中,小鼠nm23基因的表达水平与转移潜能呈负相关。在具有高转移潜能的人类乳腺癌中,人nm23同源物的表达也低于低转移潜能的乳腺癌。在本研究中,我们检测了18对匹配的人正常结肠组织和肿瘤组织中nm23表达在结肠癌发生过程中的变化。我们发现,在形态学上正常的结肠黏膜的所有样本中均表达一种0.8千碱基的nm23转录本。在18个结肠肿瘤中的16个中,与同一个体形态学上正常的结肠黏膜相比,肿瘤组织中nm23的表达进一步增加。在3个息肉中的3个、3个非转移性癌中的2个以及12个初次就诊时即发生转移的癌中的11个中,nm23的表达高于正常黏膜。在12个转移性结肠肿瘤和6个临床分期较低的结肠肿瘤中,nm23的表达水平相似。此外,从人结肠肿瘤起始的12个细胞系中的每一个在培养中nm23表达均得以维持,并且在由高转移能力或低转移能力肿瘤建立的细胞系之间没有差异。我们得出结论,nm23在正常结肠黏膜中表达。nm23的表达在结肠癌发生的早期阶段增加,并在转移性结肠癌中持续增加。因此,在结肠中,组织特异性事件使nm23表达与肿瘤转移能力的丧失相分离。