The Contribution of Hypoxia-Inducible Factor (HIF)-1a to Normal Mammary Gland Development and Mammary Tumorigenesis
Abstract
During pregnancy the mammary epithelium and its supporting vasculature rapidly expand to prepare for lactation. To investigate the role of oxygenation and metabolism in these processes the oxygen-responsive component of the hypoxia-inducible factor (HIF)-l complex, HIF-1a, was deleted in the murine mammary gland using the Cre/loxP system. Although vascular density remained similar, loss of HIF-1a impaired mammary differentiation and lipid metabolism, culminating in lactation failure and changes in milk composition. Reduced expression of classical HIF- 1 target genes as well as multiple markers of differentiation were observed. Transplantation experiments confirmed that these developmental defects were epithelial cell-autonomous. Based on these novel results, we suggest that HIF- la plays a critical role in the differentiation and function of the mammary epithelium.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2002
- Accession Number
- ADA411548
Entities
People
- Randall S. Johnson
- Tiffany N Seagroves
Organizations
- University of California, San Diego