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Derivation of Thymic Lymphoma T-cell Lines from Atm-/- and p53-/- Mice
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Targeted deletion of p73 in mice reveals its role in T cell development and lymphomagenesis

Alice Nemajerova1, Gustavo Palacios, Norma J Nowak

  • 1Department of Pathology, State University of New York at Stony Brook, Stony Brook, NY, USA.

Plos One
|November 13, 2009
PubMed

Insights

The p73 gene acts as a T cell tumor suppressor. Loss of p73, alongside p53, accelerates T cell lymphoma development and progression in mice.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Transcriptional silencing of the p73 gene via methylation is observed in human leukemias and lymphomas.
  • The specific role of p73 in cancer development requires further investigation.

Purpose of the Study:

  • To investigate the function of the p73 gene in T cell lymphoma development.
  • To determine if p73 acts as a tumor suppressor in a T cell context.

Main Methods:

  • Utilized a genetically defined mouse model to study T cell lymphoma.
  • Compared lymphoma incidence and progression in mice with p53 loss versus combined p53 and p73 loss.

Main Results:

  • p73 functions as a T cell-specific tumor suppressor.
  • Concomitant loss of p53 and p73 significantly increases thymic lymphoma incidence and promotes aggressive disease.
  • Tumorigenesis in p53/p73 deficient mice involves altered gene expression, impaired T cell development, defective apoptosis, and chromosomal instability.

Conclusions:

  • Loss of p73 is causally linked to the progression of T cell lymphomas.
  • The tumor-suppressive functions of p73 are context-dependent, playing a critical role in T cell development and preventing neoplasia.

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