Modulation of Glucose Transporter 1 (GLUT1) Expression Levels Alters Mouse Mammary Tumor Cell Growth In Vitro and In Vivo

Christian D Young; Andrew S Lewis; Michael C Rudolph; Marisa D Ruehle; Matthew R Jackman; Ui J Yun; Olesya Ilkun; Renata Pereira; E. Dale Abel; Steven M Anderson

doi:10.1371/journal.pone.0023205

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Modulation of Glucose Transporter 1 (GLUT1) Expression Levels Alters Mouse Mammary Tumor Cell Growth In Vitro and In Vivo

Journal article

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Modulation of Glucose Transporter 1 (GLUT1) Expression Levels Alters Mouse Mammary Tumor Cell Growth In Vitro and In Vivo

Christian D Young, Andrew S Lewis, Michael C Rudolph, Marisa D Ruehle, Matthew R Jackman, Ui J Yun, Olesya Ilkun, Renata Pereira, E. Dale Abel and Steven M Anderson

PloS one, Vol.6(8), pp.e23205-e23205

2011

DOI: 10.1371/journal.pone.0023205

PMCID: PMC3149640

PMID: 21826239

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Abstract

Tumor cells exhibit an altered metabolism characterized by elevated aerobic glycolysis and lactate secretion which is supported by an increase in glucose transport and consumption. We hypothesized that reducing or eliminating the expression of the most prominently expressed glucose transporter(s) would decrease the amount of glucose available to breast cancer cells thereby decreasing their metabolic capacity and proliferative potential. Of the 12 GLUT family glucose transporters expressed in mice, GLUT1 was the most abundantly expressed at the RNA level in the mouse mammary tumors from MMTV-c-ErbB2 mice and cell lines examined. Reducing GLUT1 expression in mouse mammary tumor cell lines using shRNA or Cre/Lox technology reduced glucose transport, glucose consumption, lactate secretion and lipid synthesis in vitro without altering the concentration of ATP, as well as reduced growth on plastic and in soft agar. The growth of tumor cells with reduced GLUT1 expression was impaired when transplanted into the mammary fat pad of athymic nude mice in vivo. Overexpression of GLUT1 in a cell line with low levels of endogenous GLUT1 increased glucose transport in vitro and enhanced growth in nude mice in vivo as compared to the control cells with very low levels of GLUT1. These studies demonstrate that GLUT1 is the major glucose transporter in mouse mammary carcinoma models overexpressing ErbB2 or PyVMT and that modulation of the level of GLUT1 has an effect upon the growth of mouse mammary tumor cell lines in vivo.

Medicine

Biology

Details

Title: Subtitle: Modulation of Glucose Transporter 1 (GLUT1) Expression Levels Alters Mouse Mammary Tumor Cell Growth In Vitro and In Vivo
Creators: Christian D Young
Andrew S Lewis - University of Colorado Anschutz Medical Campus
Michael C Rudolph
Marisa D Ruehle
Matthew R Jackman
Ui J Yun
Olesya Ilkun
Renata Pereira
E. Dale Abel
Steven M Anderson
Resource Type: Journal article
Publication Details: PloS one, Vol.6(8), pp.e23205-e23205
DOI: 10.1371/journal.pone.0023205
PMID: 21826239
PMCID: PMC3149640
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: Public Library of Science; San Francisco, USA
Alternative title: GLUT1 Is Required for Mammary Tumor Growth
Language: English
Date published: 2011
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984025284702771

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