Activator protein 2alpha suppresses intestinal tumorigenesis in the Apc(min) mouse

Qingjie Li1, Christiane V Löhr, Roderick H Dashwood

  • 1Linus Pauling Institute, Oregon State University, Corvallis, OR 97331-6512, USA.

Cancer Letters
|April 21, 2009
PubMed

Insights

Activator protein 2alpha (AP-2alpha) acts as a tumor suppressor. Gene delivery of AP-2alpha inhibited intestinal polyp formation in mice, supporting its therapeutic potential for cancers with Wnt pathway dysregulation.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Activator protein 2alpha (AP-2alpha) is a potential tumor suppressor.
  • Reduced AP-2alpha expression is observed in various cancers, including melanoma, prostate, breast, and colon cancers.
  • AP-2alpha was previously shown to inhibit beta-catenin/T-cell factor-4 (TCF-4) transcriptional activity in colorectal cancer cells.

Purpose of the Study:

  • To investigate the in vivo tumor suppressor role of AP-2alpha in the gastrointestinal tract.
  • To explore AP-2alpha as a potential therapeutic target for cancers with Wnt signaling pathway dysregulation.

Main Methods:

  • In vivo gene delivery of AP-2alpha into Apc(min) mice.
  • Immunoblot analyses and immunohistochemistry to assess AP-2alpha expression.
  • Co-immunoprecipitation assays to study protein interactions.

Main Results:

  • Gene delivery of AP-2alpha suppressed intestinal polyp formation in Apc(min) mice.
  • AP-2alpha delivery led to increased AP-2alpha expression in mouse intestinal mucosa and liver.
  • Evidence of interactions between AP-2alpha, beta-catenin, and adenomatous polyposis coli (APC) proteins was found in mouse and human colorectal cancer samples.

Conclusions:

  • AP-2alpha demonstrates a tumor suppressor role in the gastrointestinal tract.
  • AP-2alpha represents a novel therapeutic target for human cancers with dysregulated Wnt signaling.

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