Targeting the PyMT Oncogene to Diverse Mammary Cell Populations Enhances Tumor Heterogeneity and Generates Rare Breast Cancer Subtypes

Brittni A. Smith, Dawne N. Shelton, Collin Kieffer, Brett Milash, Jerry Usary, Charles M. Perou, Philip S. Bernard, Bryan E. Welm

Research output: Contribution to journalArticle

Abstract

Human breast cancer is a heterogeneous disease composed of different histologies and molecular subtypes, many of which are not replicated in animal models. Here, we report a mouse model of breast cancer that generates unique tumor histologies including tubular, adenosquamous, and lipid-rich carcinomas. Utilizing a nononcogenic variant of polyoma middle T oncogene (PyMT) that requires a spontaneous base-pair deletion to transform cells, in conjunction with lentiviral transduction and orthotopic transplantation of primary mammary epithelial cells, this model sporadically induces oncogene expression in both the luminal and myoepithelial cell lineages of the normal mouse mammary epithelium. Microarray and hierarchical analyses using an intrinsic subtype gene set revealed that lentiviral PyMT generates both luminal and basal-like tumors. Cumulatively, these results show that low-level expression of PyMT in a broad range of cell types significantly increases tumor heterogeneity and establishes a mouse model of several rare human breast cancer subtypes.

Original languageEnglish (US)
Pages (from-to)550-563
Number of pages14
JournalGenes and Cancer
Volume3
Issue number9-10
DOIs
StatePublished - Dec 1 2012

Keywords

  • PyMT
  • breast cancer
  • cell of origin
  • lipid rich
  • mammary gland

ASJC Scopus subject areas

  • Genetics
  • Cancer Research

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