Department of Digestive Surgery, Saitama International Medical Center, Saitama Medical University, Saitama, Japan.
Cancer Sci. 2012 Jul;103(7):1267-71. doi: 10.1111/j.1349-7006.2012.02300.x. Epub 2012 May 17.
Arm protein lost in epithelial cancers, on chromosome X (ALEX; also known as armadillo repeat containing, X-linked [ARMCX]) is a novel subgroup within the armadillo (ARM) family, which has several ARM repeat domains. The biological function of classical ARM family members such as β-catenin is well understood, but that of the ALEX/ARMCX family members is largely unknown. Here we evaluate the effects of ALEX1 overexpression on in vitro colony formation ability and expression of ALEX1 mRNA in human colorectal tumor. Overexpression of ALEX1 suppressed the anchorage-dependent and -independent colony formation of human colorectal carcinoma cell lines by the study of stable clones of HCT116 cells expressing ALEX1 protein. Bisulfite genomic sequencing revealed that the promoter region of ALEX1 gene was highly methylated in both HCT116 and SW480 cells in comparison with PANC-1 and MCF-7 cells, which express endogenous ALEX1 mRNA, indicating the capability of promoter methylation to silence ALEX1 gene in HCT116 and SW480 cells. Our current findings suggest that overexpression of ALEX1 play a negative role in human colorectal tumorigenesis.
X 染色体上的上皮性肿瘤缺失的臂蛋白（ALEX；也称为富含角蛋白重复序列的 X 连锁蛋白 [ARMCX]）是角蛋白（ARM）家族中的一个新亚群，具有多个 ARM 重复结构域。β-连环蛋白等经典 ARM 家族成员的生物学功能已得到很好的理解，但 ALEX/ARMCX 家族成员的生物学功能在很大程度上仍是未知的。在此，我们评估了 ALEX1 过表达对体外集落形成能力的影响，并检测了人结直肠肿瘤中 ALEX1 mRNA 的表达。通过对表达 ALEX1 蛋白的 HCT116 细胞的稳定克隆的研究，发现 ALEX1 的过表达抑制了人结直肠癌细胞系的锚定依赖性和非依赖性集落形成。亚硫酸氢盐基因组测序显示，与表达内源性 ALEX1 mRNA 的 PANC-1 和 MCF-7 细胞相比，ALEX1 基因的启动子区域在 HCT116 和 SW480 细胞中高度甲基化，表明启动子甲基化有能力沉默 HCT116 和 SW480 细胞中的 ALEX1 基因。我们目前的研究结果表明，ALEX1 的过表达在人结直肠肿瘤发生中起负性作用。
