ITF-2, a downstream target of the Wnt/TCF pathway, is activated in human cancers with β-catenin defects and promotes neoplastic transformation
ITF-2, a downstream target of the Wnt/TCF pathway, is activated in human cancers with β-catenin defects and promotes neoplastic transformation
复制标题
DOI：
10.1016/s1535-6108(02)00035-1
复制
发表时间：
2002-03-01
期刊：
影响因子：
50.3
通讯作者：
Fearon, ER
中科院分区：
文献类型：
--
作者：
Kolligs, FT;Nieman, MT;Fearon, ER
在许多癌症中，腺瘤性结肠息肉病（APC）或Axin肿瘤抑制蛋白的失活或β-连环蛋白的激活突变导致β-连环蛋白水平升高，β-连环蛋白与T细胞因子（TCF）蛋白的结合增强，以及TCF调节基因的表达增加。我们发现，在大鼠E1 A永生化RK 3E细胞中，碱性螺旋-环-螺旋转录因子ITF-2（免疫球蛋白转录因子-2）的基因在β-连环蛋白或配体诱导的β-连环蛋白-雌激素受体融合蛋白激活的肿瘤转化后被激活。具有β-连环蛋白调节缺陷的人类癌症具有升高的ITF-2表达，并且通过恢复野生型APC功能或抑制TCF活性来抑制ITF-2。值得注意的是，ITF-2促进了芸香细胞的肿瘤转化。我们认为ITF-2是一个TCF调节基因，它与其他TCF靶基因一起发挥作用，以促进β-连环蛋白调节缺陷的癌细胞的生长和/或存活。
In many cancers, inactivation of the adenomatous polyposis coli (APC) or Axin tumor suppressor proteins or activating mutations in beta-catenin lead to elevated beta-catenin levels, enhanced binding of beta-catenin to T cell factor (TCF) proteins, and increased expression of TCF-regulated genes. We found that the gene for the basic helix-loop-helix transcription factor ITF-2 (immunoglobulin transcription factor-2) was activated in rat E1A-immortalized RK3E cells following neoplastic transformation by beta-catenin or ligand-induced activation of a beta-catenin-estrogen receptor fusion protein. Human cancers with beta-catenin regulatory defects had elevated ITF-2 expression, and ITF-2 was repressed by restoring wild-type APC function or inhibiting TCF activity. Of note, ITF-2 promoted neoplastic transformation of RUE cells. We propose that ITF-2 is a TCF-regulated gene, which functions in concert with other TCF target genes to promote growth and/or survival of cancer cells with defects in beta-catenin regulation.