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Altered glucose metabolism in Harvey‐ ras transformed MCF10A cells
Author(s) -
Zheng Wei,
Tayyari Fariba,
Gowda G.A. Nagana,
Raftery Daniel,
McLamore Eric S.,
Porterfield D. Marshall,
Donkin Shawn S.,
Bequette Brian,
Teegarden Dorothy
Publication year - 2015
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.22079
Subject(s) - biology , pentose phosphate pathway , carcinogenesis , oncogene , glycolysis , warburg effect , citric acid cycle , metabolism , biochemistry , carbohydrate metabolism , glut1 , flux (metallurgy) , metabolite , metabolome , glucose uptake , microbiology and biotechnology , cell cycle , cell , endocrinology , chemistry , insulin , gene , organic chemistry
Metabolic reprogramming that alters the utilization of glucose including the “Warburg effect” is critical in the development of a tumorigenic phenotype. However, the effects of the Harvey‐ ras (H‐ ras ) oncogene on cellular energy metabolism during mammary carcinogenesis are not known. The purpose of this study was to determine the effect of H‐ ras transformation on glucose metabolism using the untransformed MCF10A and H‐ ras oncogene transfected (MCF10A‐ ras ) human breast epithelial cells, a model for early breast cancer progression. We measured the metabolite fluxes at the cell membrane by a selective micro‐biosensor, [ 13 C 6 ]glucose flux by 13 C‐mass isotopomer distribution analysis of media metabolites, intracellular metabolite levels by NMR, and gene expression of glucose metabolism enzymes by quantitative PCR. Results from these studies indicated that MCF10A‐ ras cells exhibited enhanced glycolytic activity and lactate production, decreased glucose flux through the tricarboxylic acid (TCA) cycle, as well as an increase in the utilization of glucose in the pentose phosphate pathway (PPP). These results provide evidence for a role of H‐ ras oncogene in the metabolic reprogramming of MCF10A cells during early mammary carcinogenesis. © 2013 Wiley Periodicals, Inc.