Suzuki H, Romano-Spica V, Papas T S, Bhat N K
Laboratory of Molecular Oncology, National Cancer Institute, Frederick, MD 21702-1201, USA.
Proc Natl Acad Sci U S A. 1995 May 9;92(10):4442-6. doi: 10.1073/pnas.92.10.4442.
We have ectopically expressed transcription factor ETS1 in two different highly tumorigenic human colon cancer cell lines, DLD-1 and HCT116, that do not express endogenous ETS1 protein and have obtained several independent clones. The expression of wild-type ETS1 protein in these colon cancer cells reverses the transformed phenotype and tumorigenicity in a dose-dependent manner. By contrast, expression in DLD-1 cells of a variant form of ETS1, lacking transcriptional activity, did not alter the tumorigenic properties of the cells, suggesting that the reduction in tumorigenicity in these clones was specific for the wild-type ETS1 gene products. Since these colon cancer cells have multiple genetic alterations, the system described in this paper could be a good model to study the suppression of tumorigenicity at a transcriptional level, which could lead to the design and development of novel drugs for cancer treatment.
我们在两种不同的高致瘤性人结肠癌细胞系DLD-1和HCT116中异位表达了转录因子ETS1，这两种细胞系不表达内源性ETS1蛋白，并获得了多个独立克隆。野生型ETS1蛋白在这些结肠癌细胞中的表达以剂量依赖的方式逆转了转化表型和致瘤性。相比之下，缺乏转录活性的ETS1变体形式在DLD-1细胞中的表达并未改变细胞的致瘤特性，这表明这些克隆中致瘤性的降低是野生型ETS1基因产物所特有的。由于这些结肠癌细胞有多种基因改变，本文描述的系统可能是一个研究转录水平上肿瘤发生抑制的良好模型，这可能会导致设计和开发用于癌症治疗的新型药物。
