Loss of adenomatous polyposis coli gene function disrupts thymic development

Fotini Gounari, Rui Chang, Janet Cowan, Zhuyan Guo, Marei Dose, Elias Gounaris, Khashayarsha Khazaie

Research output: Contribution to journalArticlepeer-review

83 Scopus citations

Abstract

Loss of the adenomatous polyposis coli (APC) protein is a common initiating event in colon cancer. Here we show that thymocyte-specific loss of APC deregulated β-catenin signaling and suppressed Notch-dependent transcription. These events promoted the proliferation of cells of the double-negative 3 and 4 stages and reduced rearrangements between the variable, diversity and joining regions of the gene encoding T cell receptor (TCR) β, encouraging developmental progression of aberrant thymocytes lacking pre-TCR and αβ TCR. Simultaneously, the loss of APC prolonged the mitotic metaphase-to-anaphase checkpoint and impaired chromosome segregation, blocking development beyond the double-negative 4 stage. The result was extensive thymic atrophy and increased frequencies of thymocytes with chromosomal abnormalities. Thus, loss of APC in immature thymocytes has consequences distinct from those of deregulation of β-catenin signaling and is essential for T cell differentiation.

Original languageEnglish (US)
Pages (from-to)800-809
Number of pages10
JournalNature immunology
Volume6
Issue number8
DOIs
StatePublished - Aug 2005

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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