Accession Number:

ADB264736

Title:

Regulation of Glucose Transport in Quiescent, Lactating, and Neoplastic Mammary Epithelia

Descriptive Note:

Final rept. 9 Sep 1996-8 Sep 2000

Corporate Author:

WASHINGTON UNIV ST LOUIS MO

Personal Author(s):

Report Date:

2000-10-01

Pagination or Media Count:

173.0

Abstract:

Glucose is a key substrate for lactating and neoplastic mammary epithelial cells. Our purpose is to understand how lactating breast meets its need for glucose transport into Golgi, the site of lactose synthesis, and whether this mechanism has physiological, pathophysiological, or potentially therapeutic relevance in breast cancer. The scope of the research includes established cell lines, primary cells, and mammary glands, from both mice and humans. Major findings are 1 in mouse and human mammary epithelial cells in culture and also in mouse mammary gland, the hormonal milieu of lactation induces GLUT1 and causes it to be targeted to Golgi, 2 GLUT1 targeting to Golgi is dynamic, rapidly reversible, and requires endocytosis, and 3 GLUT1 is virtually absent from the plasma membrane in MCF7 and MDA231 cancer cells even in the absence of lactogenic hormones, and is targeted to a non-Golgi compartment. The results suggest that GLUT1 is not responsible for plasma membrane glucose transport activity in breast cancer. A unique mechanism, possibly with effects on targeting and activity of other proteins, must underlie the sequestration of GLUT1 in breast cancer cells. These cells may express a novel glucose transporter, potentially an attractive therapeutic target.

Subject Categories:

  • Biochemistry
  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE