Accession Number:

ADA411548

Title:

The Contribution of Hypoxia-Inducible Factor (HIF)-1a to Normal Mammary Gland Development and Mammary Tumorigenesis

Descriptive Note:

Annual rept. 1 Oct 2001-30 Sep 2002

Corporate Author:

CALIFORNIA UNIV SAN DIEGO LA JOLLA

Report Date:

2002-10-01

Pagination or Media Count:

61.0

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 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.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE