Pathologisches Institut der Ludwig-Maximilians-Universität, München, Germany.
Cell Cycle. 2012 Sep 1;11(17):3331-8. doi: 10.4161/cc.21790. Epub 2012 Aug 16.
The majority of colorectal cancers (CRCs) are characterized by a dysregulated canonical Wnt-signaling pathway leading to the stabilization and subsequent cellular increase and accumulation of β-catenin. After translocation into the nucleus, it acts as a transcription factor resulting in the expression of β-catenin target genes. These resemble most of the hallmarks of cancer except eternal life. The central mediator of this hallmark is hTERT (human telomerase reverse transcriptase). The hTERT gene is regulated, besides others, by the transcription factor c-Myc and, thus, indirectly via β-catenin as c-Myc is a β-catenin target gene. Interestingly, the expression patterns of hTERT and β-catenin, but not c-Myc are overlapping, probably because c-Myc is not only regulated by β-catenin, but also by many other transcription factors and pathways. Therefore, we argued that hTERT might be a direct target gene of β-catenin. In this study, we show evidence that β-catenin directly regulates the expression of the hTERT gene.
大多数结直肠癌(CRC)的特征是调控失常的经典 Wnt 信号通路,导致β-连环蛋白的稳定和随后的细胞增加和积累。β-连环蛋白易位进入细胞核后,作为转录因子发挥作用,导致β-连环蛋白靶基因的表达。这些基因类似于大多数癌症的特征,除了永生。这个特征的核心介质是 hTERT(人端粒酶逆转录酶)。hTERT 基因除了其他基因外,还受到转录因子 c-Myc 的调控,因此,间接通过β-连环蛋白调控,因为 c-Myc 是β-连环蛋白的靶基因。有趣的是,hTERT 和β-连环蛋白的表达模式重叠,但 c-Myc 的表达模式不重叠,可能是因为 c-Myc 不仅受β-连环蛋白调控,还受许多其他转录因子和途径调控。因此,我们认为 hTERT 可能是β-连环蛋白的直接靶基因。在这项研究中,我们证明了β-连环蛋白可以直接调控 hTERT 基因的表达。