title: Altered glucose metabolism in Harvey-ras transformed MCF10A cells.
abstract: 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)C6 ]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.
authors.affiliation: Interdepartmental Nutrition Program, Purdue University, West Lafayette, Indiana, 47906.
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.forename: Fariba
authors.initials: F
authors.lastname: Tayyari
authors.forename: G A Nagana
authors.initials: GA
authors.lastname: Gowda
authors.forename: Daniel
authors.initials: D
authors.lastname: Raftery
authors.forename: Eric S
authors.initials: ES
authors.lastname: McLamore
authors.forename: D Marshall
authors.initials: DM
authors.lastname: Porterfield
authors.forename: Shawn S
authors.initials: SS
authors.lastname: Donkin
authors.forename: Brian
authors.initials: B
authors.lastname: Bequette
authors.forename: Dorothy
authors.initials: D
authors.lastname: Teegarden
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D002952:Citric Acid Cycle; D004734:Energy Metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics* / Q000378:metabolism
chemical_list: D019344:Lactic Acid; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras); D005947:Glucose
keywords: breast cancer; glucose; metabolism; ras