Nestl A, Von Stein O D, Zatloukal K, Thies W G, Herrlich P, Hofmann M, Sleeman J P
Forschungszentrum Karlsruhe, Institute of Toxicology and Genetics, Germany.
Cancer Res. 2001 Feb 15;61(4):1569-77.
Using subtractive technology, we have generated metastasis-associated gene expression profiles for rat mammary and pancreatic adenocarcinomas. Several genes whose expression is thought to be related to tumor progression such as c-Met, urokinase-type plasminogen activator receptor, ezrin, HMG-1, oncomodulin, cathepsin, and caveolin were thereby isolated. Half of the metastasis-associated clones showed no significant homology to genes with known function. Notably, several of the metastasis-associated clones were also expressed in metastatic lines but not in nonmetastatic lines of other tumor models. Furthermore, in situ hybridization using selected clones documents the relevance of these results for human cancer because strong expression in tumor cells including metastases was detected in human colorectal cancer samples and, to a lesser extent, in mammary cancer samples. These data support the concept that tumors express a "metastatic program" of genes.
利用消减技术，我们已生成大鼠乳腺和胰腺腺癌的转移相关基因表达谱。由此分离出了几个其表达被认为与肿瘤进展相关的基因，如c-Met、尿激酶型纤溶酶原激活物受体、埃兹蛋白、高迁移率族蛋白1、癌调蛋白、组织蛋白酶和小窝蛋白。一半的转移相关克隆与已知功能的基因无明显同源性。值得注意的是，一些转移相关克隆也在其他肿瘤模型的转移细胞系中表达，但不在非转移细胞系中表达。此外，使用选定克隆进行的原位杂交证明了这些结果与人类癌症的相关性，因为在人类结直肠癌样本中检测到肿瘤细胞包括转移灶中有强表达，在乳腺癌样本中的表达程度较低。这些数据支持肿瘤表达基因“转移程序”这一概念。
