Identification of c-MYC as a Target of the APC Pathway
TC He, AB Sparks, C Rago, H Hermeking, L Zawel… - Science, 1998 - science.org
Science, 1998•science.org
The adenomatous polyposis coli gene (APC) is a tumor suppressor gene that is inactivated
in most colorectal cancers. Mutations of APC cause aberrant accumulation of β-catenin,
which then binds T cell factor–4 (Tcf-4), causing increased transcriptional activation of
unknown genes. Here, the c-MYC oncogene is identified as a target gene in this signaling
pathway. Expression of c-MYC was shown to be repressed by wild-type APC and activated
by β-catenin, and these effects were mediated through Tcf-4 binding sites in the c-MYC …
in most colorectal cancers. Mutations of APC cause aberrant accumulation of β-catenin,
which then binds T cell factor–4 (Tcf-4), causing increased transcriptional activation of
unknown genes. Here, the c-MYC oncogene is identified as a target gene in this signaling
pathway. Expression of c-MYC was shown to be repressed by wild-type APC and activated
by β-catenin, and these effects were mediated through Tcf-4 binding sites in the c-MYC …
The adenomatous polyposis coli gene (APC) is a tumor suppressor gene that is inactivated in most colorectal cancers. Mutations of APC cause aberrant accumulation of β-catenin, which then binds T cell factor–4 (Tcf-4), causing increased transcriptional activation of unknown genes. Here, the c-MYC oncogene is identified as a target gene in this signaling pathway. Expression of c-MYC was shown to be repressed by wild-type APC and activated by β-catenin, and these effects were mediated through Tcf-4 binding sites in the c-MYC promoter. These results provide a molecular framework for understanding the previously enigmatic overexpression of c-MYC in colorectal cancers.
AAAS