HIF1α is a critical regulator of secretory differentiation and activation, but not vascular expansion, in the mouse mammary gland

Tiffany N. Seagroves, Darryl Hadsell, Jim McManaman, Carol Palmer, Debbie Liao, Wayne McNulty, Bryan Welm, Kay Uwe Wagner, Margaret Neville, Randall S. Johnson

Research output: Contribution to journalReview article

62 Scopus citations

Abstract

During pregnancy the mammary epithelium and its supporting vasculature rapidly expand to prepare for lactation, resulting in dramatic changes in the micro-environment. In order to investigate the role of oxygenation and metabolism in these processes, the oxygen-responsive component of the hypoxia-inducible factor (HIF) 1 complex, HIF1α, was deleted in the murine mammary gland. Although vascular density was unchanged in the HIF1α null mammary gland, loss of HIF1α impaired mammary differentiation and lipid secretion, culminating in lactation failure and striking changes in milk composition. Transplantation experiments confirmed that these developmental defects were mammary epithelial cell autonomous. These data make clear that HIF1α plays a critical role in the differentiation and function of the mammary epithelium.

Original languageEnglish (US)
Pages (from-to)1713-1724
Number of pages12
JournalDevelopment
Volume130
Issue number8
DOIs
StatePublished - Apr 2003

Keywords

  • Differentiation
  • HIF1
  • Hypoxia
  • Lactation
  • Mammary gland
  • Metabolism
  • Mouse

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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    Seagroves, T. N., Hadsell, D., McManaman, J., Palmer, C., Liao, D., McNulty, W., Welm, B., Wagner, K. U., Neville, M., & Johnson, R. S. (2003). HIF1α is a critical regulator of secretory differentiation and activation, but not vascular expansion, in the mouse mammary gland. Development, 130(8), 1713-1724. https://doi.org/10.1242/dev.00403