The β-catenin binding domain of adenomatous polyposis coli is sufficient for tumor suppression

Research output: Contribution to journalArticle

Abstract

Inactivation of the adenomatous polyposis coli (APC) gene is a critical event in the development of human colorectal cancers. At the biochemical level, several functions have been assigned to the multidomain APC protein, but the cellular effects of APC expression and how they relate to its biochemical functions are less well-defined. To address these issues, we generated a recombinant adenovirus (Ad-CBR) that constitutively expresses the central third of APC, which includes all of the known β-catenin binding repeats. When expressed in colon cancer cells, Ad-CBR blocked the nuclear translocation of β-catenin and inhibited β-catenin/Tcf-4-mediated transactivation. Accordingly, expression of endogenous targets of the APC/β- catenin/Tcf-4 pathway was down-regulated. AdCBR infection of colorectal cancer cell lines with mutant APC but wild-type β-catenin resulted in substantial growth arrest followed by apoptosis. These effects were attenuated in lines with wild-type APC but with mutated β-catenin. These findings suggest that the β-catenin-binding domain in the central third of APC is sufficient for its tumor suppressor activity.

Original languageEnglish (US)
Pages (from-to)1671-1676
Number of pages6
JournalCancer Research
Volume60
Issue number6
StatePublished - Mar 15 2000

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Catenins
Adenomatous Polyposis Coli
Neoplasms
Colorectal Neoplasms
Adenomatous Polyposis Coli Protein
APC Genes
Human Development
Adenoviridae
Colonic Neoplasms
Transcriptional Activation
Apoptosis
Cell Line
Growth
Infection

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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The β-catenin binding domain of adenomatous polyposis coli is sufficient for tumor suppression. / Shih, Ie Ming; Yu, Jian; He, Tong Chuan; Vogelstein, Bert; Kinzler, Kenneth W.

In: Cancer Research, Vol. 60, No. 6, 15.03.2000, p. 1671-1676.

Research output: Contribution to journalArticle

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