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Genomic analyses as a guide to target identification and preclinical testing of mouse models of breast cancer

Christina N Bennett1, Jeffrey E Green

  • 1Laboratory of Cancer Biology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA.

Toxicologic Pathology
|January 19, 2010
PubMed

Insights

Cross-species genomic analysis identified a gene network in mouse models that mirrors human triple-negative breast cancer. This network may reveal new therapeutic targets for this aggressive cancer subtype.

Area of Science:

  • Genomics
  • Cancer Biology
  • Translational Oncology

Background:

  • Cross-species genomic analyses reveal conserved alterations in human cancers and mouse models.
  • High-throughput molecular analyses aid in selecting relevant animal models for human cancer subtypes.
  • Conserved gene copy number and expression changes suggest critical roles in cancer development and therapeutic potential.

Purpose of the Study:

  • To identify molecular features of human triple-negative breast cancer using cross-species analysis.
  • To discover a genetic network associated with poor outcomes in human epithelial cancers.
  • To explore potential therapeutic targets for triple-negative breast cancer.

Main Methods:

  • Utilized cross-species analysis of mouse models with disrupted p53, Rb, and BRCA1 functions.
  • Employed targeted abrogation of p53 and Rb function in mouse tumor models.
  • Identified an integrated genetic network correlating with poor prognosis in human epithelial cancers.

Main Results:

  • Mouse models with disrupted p53, Rb, and BRCA1 functions exhibit molecular characteristics of human triple-negative, basal-type breast cancer.
  • A large, integrated genetic network associated with poor outcomes in human epithelial cancers was identified.
  • The identified gene signature is enriched for genes involved in DNA replication, repair, chromosome maintenance, cell cycle regulation, and apoptosis.

Conclusions:

  • Mouse models accurately recapitulate key molecular features of human triple-negative breast cancer.
  • The identified gene network represents a potential therapeutic avenue for aggressive epithelial cancers.
  • Further research aims to validate specific gene targets within this network for novel triple-negative breast cancer therapies.

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