Target disruption of the mutant β-catenin gene in colon cancer cell line HCT116:: preservation of its malignant phenotype
Target disruption of the mutant β-catenin gene in colon cancer cell line HCT116:: preservation of its malignant phenotype
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DOI：
10.1038/sj.onc.1205756
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发表时间：
2002-08-29
期刊：
影响因子：
8
通讯作者：
Hirohashi, S
中科院分区：
文献类型：
--
作者：
Sekine, S;Shibata, T;Hirohashi, S
大多数结直肠癌都存在导致β-连环蛋白稳定的基因改变。通过同源重组改造结直肠癌细胞系 HCT116，该细胞系同时具有突变型和野生型 β-catenin 基因，以研究 β-catenin 基因突变的意义。正如预期的那样，突变等位基因靶向克隆表现出 β-连环蛋白表达降低和 T 细胞因子 (TCF)/淋巴增强因子 (LEF) 依赖性转录下调。在形态学上，靶向克隆在通常的培养条件下仅发生最小程度的改变，但在低血清条件下，突变等位基因靶向克隆仍然平面生长，与形成球状体的亲本细胞系和野生等位基因靶向克隆相反。突变等位基因靶向克隆在体外显示生长速率和不依赖贴壁的生长没有显着变化，并且在体内表现出相当增加的生长。尽管β-连环蛋白的稳定性会影响一些生物学特性，包括粘附特性，但它至少在某些结直肠癌中可能不具有生长促进作用。
Most colorectal carcinomas harbor genetic alterations that result in stabilization of beta-catenin. A colorectal carcinoma cell line, HCT116, which has both mutated and wild-type beta-catenin genes, was engineered by homologous recombination to investigate the significance of beta-catenin gene mutation. As expected, the mutant allele-targeted clones showed decreased beta-catenin expression and down-regulation of T-cell factor (TCF)/lymphoid enhancer factor (LEF)-dependent transcription. Morphologically, targeted clones were only minimally altered under usual culture conditions, but under low serum conditions, mutant allele-targeted clones still grew in plane, in contrast to parental cell line and wild allele-targeted clones, which formed spheroids. The mutant allele-targeted clones showed no significant changes in growth rate and anchorage-independent growth in vitro, and displayed rather increased growth in vivo. Although beta-catenin stabilization affects some biological characteristics including adhesive properties, it may not have growth-promoting effects at least in some colorectal carcinomas.