Abstract
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 beta-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 beta-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.
Publication types
-
Comment
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Adenomatous Polyposis Coli Protein
-
Binding Sites
-
Cell Line
-
Colorectal Neoplasms / genetics*
-
Cytoskeletal Proteins / genetics
-
Cytoskeletal Proteins / metabolism
-
Gene Expression Regulation, Neoplastic*
-
Genes, APC*
-
Genes, Reporter
-
Genes, myc*
-
HT29 Cells
-
Humans
-
Mutation
-
Promoter Regions, Genetic
-
Proto-Oncogene Proteins c-myc / metabolism
-
Signal Transduction
-
TCF Transcription Factors
-
Trans-Activators*
-
Transcription Factor 7-Like 2 Protein
-
Transcription Factors / metabolism
-
Transcription, Genetic
-
beta Catenin
Substances
-
Adenomatous Polyposis Coli Protein
-
CTNNB1 protein, human
-
Cytoskeletal Proteins
-
Proto-Oncogene Proteins c-myc
-
TCF Transcription Factors
-
TCF7L2 protein, human
-
Trans-Activators
-
Transcription Factor 7-Like 2 Protein
-
Transcription Factors
-
beta Catenin