Regulation of Glucose Utilization by Estradiol in Breast Cancer
Abstract
Administration of estradiol (E2) to estrogen receptor-positive (ER+) breast cancer patients increases glucose uptake by tumors. Accordingly, downstream metabolic regulators of E2 are expected to have utility as targets for the development of anti-breast cancer agents. The family of 6-phosphofructo-2-kinase/fructose-2,6-bisphos-phatases (PFKFB1-4) control glycolytic flux via their product, fructose-2,6-bisphosphate (F26BP), which activates 6-phosphofructo-1-kinase (PFK-1). The goal of the proposal was to study a novel regulatory pathway for E2 induced metabolism via PFKFB3 in breast cancer cells. In the initial proposal demonstrate that exposure of human MCF-7 breast cancer cells to E2 causes a rapid increase in glucose uptake that is coincident with an induction of PFKFB3 mRNA, protein expression and the intracellular concentration of its product, F26BP. To this end, we have expanded our studies to include two additional breast cancer cell lines, T47 (ER+) and MDA-MB-231 (ER-) cells. We determined that ER directly regulates PFKFB3 expression via binding to its promoter. We examined the changes in glucose flux upon E2 administration in a PFKFB3 null and overexpression background and confirmed that E2 increases glucose uptake and glycolysis via PFKFB3. The results from our studies were published in the Journal of Biological Chemistry (see appendix 1).
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2014
- Accession Number
- ADA613311
Entities
People
- Yoannis Imbert-fernandez
Organizations
- University of Louisville