Abstract
The adenomatous polyposis coli (APC) tumor suppressor protein binds to beta-catenin, a protein recently shown to interact with Tcf and Lef transcription factors. The gene encoding hTcf-4, a Tcf family member that is expressed in colonic epithelium, was cloned and characterized. hTcf-4 transactivates transcription only when associated with beta-catenin. Nuclei of APC-/- colon carcinoma cells were found to contain a stable beta-catenin-hTcf-4 complex that was constitutively active, as measured by transcription of a Tcf reporter gene. Reintroduction of APC removed beta-catenin from hTcf-4 and abrogated the transcriptional transactivation. Constitutive transcription of Tcf target genes, caused by loss of APC function, may be a crucial event in the early transformation of colonic epithelium.
| Original language | English |
|---|---|
| Pages (from-to) | 1784-1787 |
| Number of pages | 4 |
| Journal | Science |
| Volume | 275 |
| Issue number | 5307 |
| Publication status | Published - 1997 |
Keywords
- Adenomatous Polyposis Coli Protein
- Amino Acid Sequence
- Animals
- Cell Line
- Cell Transformation, Neoplastic
- Cloning, Molecular
- Colon
- Colonic Neoplasms
- Cytoskeletal Proteins
- Gene Expression Regulation, Neoplastic
- Genes, APC
- Genes, Reporter
- Humans
- Intestinal Mucosa
- Mice
- Molecular Sequence Data
- Signal Transduction
- TCF Transcription Factors
- Trans-Activators
- Transcription Factor 7-Like 2 Protein
- Transcription Factors
- Transcriptional Activation
- Transfection
- Tumor Cells, Cultured
- beta Catenin