Parity-induced mammary epithelial cells facilitate tumorigenesis in MMTV-neu transgenic mice

Ma Linda D. Henry, Aleata A. Triplett, Keon Bong Oh, Gilbert H. Smith, Kay Uwe Wagner

Research output: Contribution to journalArticle

96 Scopus citations

Abstract

Using a Cre-lox-based genetic labeling technique, we have recently discovered a parity-induced mammary epithelial subtype that is abundant in nonlactating and nonpregnant, parous females. These mammary epithelial cells serve as alveolar progenitors in subsequent pregnancies, and transplantation studies revealed that they possess features of multipotent progenitors such as self-renewal and the capability to contribute to ductal and alveolar morphogenesis. Here, we report that these cells are the cellular targets for transformation in MMTV-neu transgenic mice that exhibit accelerated mammary tumorigenesis in multiparous animals. The selective ablation of this epithelial subtype reduces the onset of tumorigenesis in multiparous MMTV-neu transgenics. There is, however, experimental evidence to suggest that parity-induced mammary epithelial cells may not be the only cellular targets in other MMTV-promoter-based transgenic strains. In particular, the heterogeneous MMTV-wnt1 lesions predominantly express the ductal differentiation marker Nkccl that is absent in MMTV-neu-derived tumors. Our observations support the idea that tumors originate from distinctly different epithelial subtypes in selected MMTV-promoter-driven cancer models and that diverse oncogenes might exert discrete effects on particular mammary epithelial subtypes.

Original languageEnglish (US)
Pages (from-to)6980-6985
Number of pages6
JournalOncogene
Volume23
Issue number41
DOIs
StatePublished - Sep 9 2004
Externally publishedYes

Keywords

  • Cre recombinase
  • Differentiation
  • Mammary gland
  • Mouse mammary tumor virus
  • Transgenics
  • Tumorigenesis

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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  • Cite this

    Henry, M. L. D., Triplett, A. A., Oh, K. B., Smith, G. H., & Wagner, K. U. (2004). Parity-induced mammary epithelial cells facilitate tumorigenesis in MMTV-neu transgenic mice. Oncogene, 23(41), 6980-6985. https://doi.org/10.1038/sj.onc.1207827