Activator protein 2α suppresses intestinal tumorigenesis in the Apcmin mouse

Qingjie Li, Christiane V. Löhr, Roderick H. Dashwood

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Activator protein 2α (AP-2α) is a putative tumor suppressor, and various reports have described the loss or reduction of AP-2α expression in cutaneous malignant melanomas, as well as in cancers of the prostate, breast and colon. Previously, AP-2α was shown to attenuate β-catenin/T-cell factor-4 (TCF-4) nuclear interactions and β-catenin/TCF-4-dependent transcriptional activity in human colorectal cancer cells [Q. Li, R.H. Dashwood, Activator protein 2alpha associates with adenomatous polyposis coli/beta-catenin and Inhibits beta-catenin/T-cell factor transcriptional activity in colorectal cancer cells, J. Biol. Chem. 279 (2004) 45669-45675]. Here, we show that in vivo gene delivery of AP-2α suppressed intestinal polyp formation in the Apcmin mouse, and protected against the development of anemia and splenomegaly. Immunoblot analyses and immunohistochemistry following gene delivery revealed an increase in AP-2α expression in the mouse intestinal mucosa and liver. Co-immunoprecipitation experiments provided evidence for interactions between AP-2α, β-catenin, and adenomatous polyposis coli (APC) proteins in mouse intestinal mucosa, as well as in a primary human colorectal cancer. Collectively, these studies support a tumor suppressor role for AP-2α in the gastrointestinal tract, and suggest that AP-2α represents a novel target for therapeutic intervention in human cancers characterized by dysregulated Wnt signaling.

Original languageEnglish (US)
Pages (from-to)36-42
Number of pages7
JournalCancer Letters
Volume283
Issue number1
DOIs
StatePublished - Sep 28 2009
Externally publishedYes

Fingerprint

Carcinogenesis
Catenins
Transcription Factor 7-Like 2 Protein
Proteins
Colorectal Neoplasms
beta Catenin
Intestinal Mucosa
Intestinal Polyps
TCF Transcription Factors
Neoplasms
Adenomatous Polyposis Coli
Splenomegaly
Immunoprecipitation
Human Activities
Colonic Neoplasms
Genes
Gastrointestinal Tract
Anemia
Prostatic Neoplasms
Immunohistochemistry

Keywords

  • β-Catenin
  • AP-2α
  • APC
  • Cancer therapeutics
  • Wnt signaling

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Activator protein 2α suppresses intestinal tumorigenesis in the Apcmin mouse. / Li, Qingjie; Löhr, Christiane V.; Dashwood, Roderick H.

In: Cancer Letters, Vol. 283, No. 1, 28.09.2009, p. 36-42.

Research output: Contribution to journalArticle

Li, Qingjie ; Löhr, Christiane V. ; Dashwood, Roderick H. / Activator protein 2α suppresses intestinal tumorigenesis in the Apcmin mouse. In: Cancer Letters. 2009 ; Vol. 283, No. 1. pp. 36-42.
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