CDX2 is mutated in a colorectal cancer with normal APC/beta-catenin signaling

Oncogene. 1999 Sep 2;18(35):5010-4. doi: 10.1038/sj.onc.1202872.

Abstract

The majority of human colorectal cancers have elevated beta-catenin/TCF regulated transcription due to either inactivating mutations of the APC tumor suppressor gene or activating mutations of beta-catenin. Surprisingly, one commonly used colorectal cancer cell line was found to have intact APC and beta-catenin and no demonstrable beta-catenin/TCF regulated transcription. However, this line did possess a truncating mutation in one allele of CDX2, a gene whose inactivation has recently been shown to cause colon tumorigenesis in mice. Expression of CDX2 was found to be induced by restoring expression of wild type APC in a colorectal cancer cell line. These findings raise the intriguing possibility that CDX2 contributes to APC's tumor suppressive effects.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenomatous Polyposis Coli Protein
  • Alleles
  • CDX2 Transcription Factor
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism*
  • DNA Mutational Analysis
  • Gene Expression Regulation, Neoplastic*
  • Genes, Tumor Suppressor / genetics
  • Genes, Tumor Suppressor / physiology
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism
  • Homeostasis
  • Humans
  • Mutation*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Signal Transduction
  • Trans-Activators*
  • Transcriptional Activation
  • Transfection
  • Tumor Cells, Cultured
  • beta Catenin

Substances

  • Adenomatous Polyposis Coli Protein
  • CDX2 Transcription Factor
  • CTNNB1 protein, human
  • Cytoskeletal Proteins
  • Homeodomain Proteins
  • Neoplasm Proteins
  • RNA, Messenger
  • Trans-Activators
  • beta Catenin