Office of Technology Transfer – University of Michigan

Transgenic Mice with Gene Fusions

Technology #3627

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Researchers
Arul Chinnaiyan
Managed By
Ed Pagani
Assistant Director, Health Technologies 734-763-3558
Publications
Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer.
Science, Volume 644. Page 310. 2005

Background

A central aim in cancer research is to identify altered genes that are causally implicated in oncogenesis. Besides mutations, insertions, deletions and etc., there is now compelling evidence for a causal role for chromosomal rearrangements in cancer. To date, many disease-specific, recurrent chromosomal rearrangements have been characterized in hematological malignancies and mesenchymal tumors, but not in common epithelial tumors such as breast, lung, colon or prostate cancer. As prostate cancer is a leading cause of cancer-related death in American men, second only to lung cancer, the identification of recurrent gene rearrangements in prostate cancers may have profound implications for cancer drug discovery as well as for patient treatment.

Technology

Researchers at the University of Michigan have identified a recurrent gene fusion of TMPRSS2 to the ETS family members ERG and ETV1 in the majority of prostate cancers. These fusions are specific to clinically localized and advanced prostate cancer and occur in the majority of cases. In parallel, the researchers also developed a transgenic mouse model, where the portions of ERG and ETV1 found in TMPRSS2:ETS fusions are specifically over expressed in the mouse prostate. These mouse models develop prostatic intraepithelial neoplasia (PIN, a prostate cancer precursor lesion) by 12 weeks of age.

Applications and Advantages

Applications

  • Mouse model for prostate cancer research
  • Preclinical therapeutic screening and testing

Advantages

  • Unlike other commonly used prostate cancer mouse models, these mice represent an authentic oncogene driven model of human prostate cancer development
  • Utility in the pre-clinical testing of therapeutics