The Contribution of Hypoxia-Inducible Factor (HIF)-1a to Normal Mammary Gland Development and Mammary Tumorigenesis
Annual rept. 1 Oct 2001-30 Sep 2002
CALIFORNIA UNIV SAN DIEGO LA JOLLA
Pagination or Media Count:
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 CreloxP 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.
- Anatomy and Physiology
- Medicine and Medical Research