Identification of Tcf-4 as a transcriptional target of p53 signalling

Karen Rother1, Cindy Johne, Katja Spiesbach

  • 1Medizinische Klinik und Poliklinik II, Max-Bürger-Forschungszentrum, Universität Leipzig, Johannisallee 30, Leipzig D-04103, Germany.

Oncogene
|March 3, 2004
PubMed

Insights

The tumor suppressor p53 directly regulates T-cell factor (Tcf)-4, a key Wnt/beta-catenin signaling component. This finding links p53 function to colon tumor progression and proliferation control.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Genetics

Background:

  • T-cell factor (Tcf)-4 is a key transcription factor in Wnt/beta-catenin signaling.
  • The tumor suppressor p53 induces cell-cycle arrest and apoptosis.
  • Mutations in p53 and Wnt/beta-catenin pathways are implicated in tumorigenesis.

Purpose of the Study:

  • To investigate the relationship between p53 and Tcf-4.
  • To determine if p53 regulates Tcf-4 expression.
  • To elucidate the role of this interaction in colon cancer progression.

Main Methods:

  • Utilized a tet-off regulated human colon cell system to induce wild-type p53.
  • Measured Tcf-4 mRNA and protein levels post-p53 induction.
  • Assessed Tcf-4 promoter activity using a luciferase reporter assay with wild-type and mutant p53.

Main Results:

  • Wild-type p53 induction reduced Tcf-4 mRNA and protein levels.
  • Tcf-4 target gene uPAR mRNA was downregulated following p53 induction.
  • Wild-type p53 repressed Tcf-4 promoter activity, while a DNA-binding deficient p53 mutant did not.

Conclusions:

  • Identified Tcf-4 as a direct downstream target of p53.
  • Established a molecular link between p53 tumor suppressor function and Wnt/beta-catenin signaling.
  • Proposed a mechanism for p53 loss contributing to colon adenoma/carcinoma progression and highlighted the role in proliferation control across tissues.

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