Roles of HES1 and DEC2, newly identified transcriptional targets of GLI1, in pancreatic carcinogenesis.

我们通过定位于DEC2启动子-1126和-1117之间的CACCC-box样元件，确定DEC2是Hedgehog信号通路下游转录因子GLI1的直接转录靶点之一。我们还发现其中一个错配修复基因MLH1被GLI1诱导的DEC2下调。我们认为Shh-GLI1-DEC2途径可能抑制MLH1的表达，从而增强胰腺癌发生过程中的基因改变和基因组不稳定性。

We identified DEC2 as one of the direct transcriptional targets of GLI1, a downstream transcription factor of Hedgehog signaling pathway, via CACCC-box-like elements localized between -1126 and -1117 in the DEC2 promoter. We also showed that one of the mismatch repair gene MLH1 was down-regulated by GLI1-induced DEC2. We propose the possibility that Shh-GLI1-DEC2 pathway represses MLH1 expression and could enhance gene alteration and genomic instability in pancreatic carcinogenesis.