Deciphering cancer complexities in genetically engineered mice

K. Simin, R. Hill, Y. Song, Q. Zhang, R. Bash, Robert Cardiff, C. Yin, A. Xiao, K. McCarthy, T. Van Dyke

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Because the pRb pathway is disrupted in most solid human cancers, we have generated genetically engineered mouse cancer models by inactivating pRb function in several cell types, including astrocytes and mammary, prostate, ovarian, and brain choroid plexus epithelia. In every case, proliferation and apoptosis are acutely induced, predisposing to malignancy. Cell type dictates the pathways involved in tumor progression. In the astrocytoma model, we developed strategies to induce events in the adult brain, either throughout the tissue or focally. Both K-Ras activation and Pten inactivation play significant roles in progression. In the prostate model, adenocarcinoma progression depends on Pten inactivation. However, nonautonomous induction of p53 in the mesenchyme leads to evolution of both compartments, with p53 loss occurring in the mesenchyme. Thus, studies in these models continue to identify key tumorigenesis mechanisms. Furthermore, we are hopeful that the models will provide useful preclinical systems for diagnostic and therapeutic development.

Original languageEnglish (US)
Pages (from-to)283-290
Number of pages8
JournalCold Spring Harbor Symposia on Quantitative Biology
Volume70
DOIs
StatePublished - Dec 1 2005

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics

Fingerprint Dive into the research topics of 'Deciphering cancer complexities in genetically engineered mice'. Together they form a unique fingerprint.

  • Cite this

    Simin, K., Hill, R., Song, Y., Zhang, Q., Bash, R., Cardiff, R., Yin, C., Xiao, A., McCarthy, K., & Van Dyke, T. (2005). Deciphering cancer complexities in genetically engineered mice. Cold Spring Harbor Symposia on Quantitative Biology, 70, 283-290. https://doi.org/10.1101/sqb.2005.70.038