Previously, separate reports showed that expression. To investigate this, we used sh RNA-mediated knock-down of β-catenin and small-molecule inhibitors of MEK (U0126) and γ-secretase (DAPT) to individually inhibit Wnt/β-catenin, MAPK, and Notch signaling, respectively.
Alternatively, Notch signaling was inhibited by doxycycline (Dox)-induced expression of dominant-negative mastermind-like 1 (dn MAML1).
The regulatory potential of the ECRs was analyzed by luciferase-reporter assays in a panel of CRC cell lines that harbor characteristic alterations in several tumor suppressors and oncogenes (Fig.
S1 −2.3-kb ECR functions as a cell type-specific transcriptional enhancer.
This study shows that inactivation of the EPHB3 gene results from the incapacitation of a transcriptional enhancer element.
enhancer dysfunction is a consequence of defective Notch signaling, which undergoes a switch in functional importance and becomes dispensable and even tumor suppressive in the course of tumorigenesis.
Principally, malfunction of any of these could lead to faulty gene expression.