J Nutr Biochem. 2013 Sep;24(9):1616-24. doi: 10.1016/j.jnutbio.2013.02.002. Epub 2013 May 1.
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.
Copyright © 2013 Elsevier Inc. All rights reserved.
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.
Copyright © 2013 Elsevier Inc. All rights reserved.
