αE-连环蛋白基因（CTNNA1）在人类结肠癌细胞中作为一种侵袭抑制基因发挥作用。

The alphaE-catenin gene (CTNNA1) acts as an invasion-suppressor gene in human colon cancer cells.

作者信息

Vermeulen S J, Nollet F, Teugels E, Vennekens K M, Malfait F, Philippé J, Speleman F, Bracke M E, van Roy F M, Mareel M M

机构信息

Department of Radiotherapy and Nuclear Medicine, University Hospital Gent, Belgium.

出版信息

Oncogene. 1999 Jan 28;18(4):905-15. doi: 10.1038/sj.onc.1202348.

DOI:10.1038/sj.onc.1202348

PMID:10023666

Abstract

The acquisition of invasiveness is a crucial step in the malignant progression of cancer. In cancers of the colon and of other organs the E-cadherin/catenin complex, which is implicated in homotypic cell-cell adhesion as well as in signal transduction, serves as a powerful inhibitor of invasion. We show here that one allele of the alphaE-catenin (CTNNA1) gene is mutated in the human colon cancer cell family HCT-8, which is identical to HCT-15, DLD-1 and HRT-18. Genetic instability, due to mutations in the HMSH6 (also called GTBP) mismatch repair gene, results in the spontaneous occurrence of invasive variants, all carrying either a mutation or exon skipping in the second alphaE-catenin allele. The alphaE-catenin gene is therefore, an invasion-suppressor gene in accordance with the two-hit model of Knudsen for tumour-suppressor genes.

摘要

获得侵袭性是癌症恶性进展中的关键步骤。在结肠癌和其他器官的癌症中，参与同型细胞间黏附以及信号转导的E-钙黏蛋白/连环蛋白复合体是侵袭的有力抑制剂。我们在此表明，αE-连环蛋白（CTNNA1）基因的一个等位基因在人结肠癌细胞系HCT-8中发生突变，HCT-8与HCT-15、DLD-1和HRT-18相同。由于HMSH6（也称为GTBP）错配修复基因的突变导致的遗传不稳定性，会自发产生侵袭性变体，所有变体在第二个αE-连环蛋白等位基因中均携带突变或外显子跳跃。因此，根据Knudsen肿瘤抑制基因的双打击模型，αE-连环蛋白基因是一种侵袭抑制基因。