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Real-time Imaging of Myeloid Cells Dynamics in ApcMin/+ Intestinal Tumors by Spinning Disk Confocal Microscopy
05:21

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Published on: October 6, 2014

Trisomy represses Apc(Min)-mediated tumours in mouse models of Down's syndrome

Thomas E Sussan1, Annan Yang, Fu Li

  • 1Department of Physiology and The Institute for Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.

Nature
|January 4, 2008
PubMed

Insights

Individuals with Down's syndrome (trisomy 21) may have a lower incidence of intestinal tumors. Mouse models show trisomy, particularly involving the Ets2 gene, significantly reduces tumor development, suggesting a potential prophylactic effect.

Area of Science:

  • Genetics
  • Cancer Biology
  • Developmental Biology

Background:

  • Epidemiological studies on cancer incidence in Down's syndrome (trisomy 21) yield conflicting results.
  • Understanding the biological basis of cancer risk in aneuploidy is crucial.

Purpose of the Study:

  • To investigate the relationship between trisomy and intestinal tumor incidence using mouse models.
  • To determine if trisomy influences Apc(Min)-mediated intestinal tumor development.

Main Methods:

  • Utilized aneuploid mouse models (Ts65Dn, Ts1Rhr, Ms1Rhr) mimicking aspects of Down's syndrome.
  • Quantified Apc(Min)-mediated intestinal tumor numbers in these models.
  • Analyzed the role of specific genes, including Ets2, in dosage-sensitive effects on tumor development.

Main Results:

  • Trisomy for human chromosome 21 orthologues in Ts65Dn and Ts1Rhr mice significantly reduced intestinal tumor numbers.
  • Monosomy for the same genes in Ms1Rhr mice increased tumor numbers.
  • The Ets2 gene was identified as a major contributor to the dosage-sensitive effect on tumor incidence.

Conclusions:

  • Trisomy, specifically involving Ets2, confers a protective effect against intestinal tumor development.
  • Overexpression of Ets2 acts as a repressor, distinct from traditional tumor suppression.
  • Upregulation of Ets2 and related genes may offer a prophylactic effect against cancer, irrespective of ploidy.

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