title: Up-regulation of vitamin B1 homeostasis genes in breast cancer.
abstract: An increased carbon flux and exploitation of metabolic pathways for the rapid generation of biosynthetic precursors is a common phenotype observed in breast cancer. To support this metabolic phenotype, cancer cells adaptively regulate the expression of glycolytic enzymes and nutrient transporters. However, activity of several enzymes involved in glucose metabolism requires an adequate supply of cofactors. In particular, vitamin B1 (thiamine) is utilized as an essential cofactor for metabolic enzymes that intersect at critical junctions within the glycolytic network. Intracellular availability of thiamine is facilitated by the activity of thiamine transporters and thiamine pyrophosphokinase-1 (TPK-1). Therefore, the objective of this study was to establish if the cellular determinants regulating thiamine homeostasis differ between breast cancer and normal breast epithelia. Employing cDNA arrays of breast cancer and normal breast epithelial tissues, SLC19A2, SLC25A19 and TPK-1 were found to be significantly up-regulated. Similarly, up-regulation was also observed in breast cancer cell lines compared to human mammary epithelial cells. Thiamine transport assays and quantitation of intracellular thiamine and thiamine pyrophosphate established a significantly greater extent of thiamine transport and free thiamine levels in breast cancer cell lines compared to human mammary epithelial cells. Overall, these findings demonstrate an adaptive response by breast cancer cells to increase cellular availability of thiamine.
authors: Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA 30602, USA. jzastre@rx.uga.edu
authors: Jason A
authors: JA
authors: Zastre
authors: Bradley S
authors: BS
authors: Hanberry
authors: Rebecca L
authors: RL
authors: Sweet
authors: A Cary
authors: AC
authors: McGinnis
authors: Kristen R
authors: KR
authors: Venuti
authors: Michael G
authors: MG
authors: Bartlett
authors: Rajgopal
authors: R
authors: Govindarajan
mesh_terms: D001692:Biological Transport; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006706:Homeostasis; D006801:Humans; D061986:MCF-7 Cells; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D013836:Thiamin Pyrophosphokinase / Q000235:genetics / Q000378:metabolism; D013831:Thiamine / Q000494:pharmacology*; D015854:Up-Regulation
chemical_list: D026901:Membrane Transport Proteins; D033681:Mitochondrial Membrane Transport Proteins; C120043:SLC19A2 protein, human; C492291:SLC19A3 protein, human; C434255:SLC25A19 protein, human; D013836:Thiamin Pyrophosphokinase; D013831:Thiamine
keywords: Breast cancer; Metabolism; Thiamine; Transporter; Vitamin