Transgenic Mammary Epithelial Osteopontin (Spp1) Expression Induces Proliferation and Alveologenesis

Neil Hubbard, Qian J. Chen, Laura K. Sickafoose, Meghan B. Wood, Jeffrey Gregg, Ninnie M. Abrahamsson, Jesse A. Engelberg, Judith E. Walls, Alexander D Borowsky

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Osteopontin (OPN) Spp1 is involved in differentiation of the mammary gland. We engineered mice to overexpress OPN in mammary epithelium and describe an altered mammary phenotype. Three transgenic (Tg) founder lines FVB/N Tg(MMTV-Opn)(1-3BOR) were propagated after FVB/NJ pronuclear injections. Mammary glands from Tg-OPN mice compared to littermate controls showed, at 4 weeks of age, exaggerated terminal end buds; at 8 and 12 weeks, more numerous and complex ducts with increased luminal protein; and at 16 weeks, increased lobulogenesis. Lactational Tg-OPN mammary glands showed more rapid lobulogenesis and lactational changes with slower gland involution and regression following weaning. Ex vivo lobulogenesis was noticeably increased from organoids of Tg-OPN mice. Immunohistochemistry revealed cytoplasmic OPN accumulation and increased Ki-67 positive mammary epithelial cells in Tg-OPN mammary glands. OPN appears to convey a proliferative stimulus for mammary epithelial cells and alters development and differentiation. These OPN mammary overexpressing mice provide a means to study the role of OPN in cancer progression.

Original languageEnglish (US)
Pages (from-to)201-212
Number of pages12
JournalGenes and Cancer
Volume4
Issue number5-6
DOIs
StatePublished - Mar 2013

Keywords

  • flow cytometry
  • involution
  • lobulogenesis
  • mammary gland
  • organoid culture
  • osteopontin

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

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