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首页> 外文期刊>The Journal of Nutritional Biochemistry >Up-regulation of vitamin B1 homeostasis genes in breast cancer.
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Up-regulation of vitamin B1 homeostasis genes in breast cancer.

机译：乳腺癌中维生素B1稳态基因的上调。

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摘要

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
机译：为了快速产生生物合成前体，增加碳通量和利用代谢途径是乳腺癌中常见的表型。为了支持这种代谢表型，癌细胞自适应地调节糖酵解酶和营养转运蛋白的表达。但是，参与葡萄糖代谢的几种酶的活性需要足够的辅因子供应。特别地，维生素B1（硫胺素）被用作在糖酵解网络内关键连接点相交的代谢酶的必需辅因子。硫胺素转运蛋白和硫胺素焦磷酸激酶-1（TPK-1）的活性促进了硫胺素的细胞内可用性。因此，本研究的目的是确定乳腺癌和正常乳腺上皮细胞之间调节硫胺素稳态的细胞决定因素是否不同。发现利用乳腺癌和正常乳腺上皮组织的cDNA阵列，SLC19A2，SLC25A19和TPK-1被显着上调。类似地，与人乳腺上皮细胞相比，在乳腺癌细胞系中也观察到上调。与人乳腺上皮细胞相比，硫胺素转运测定法和细胞内硫胺素和焦磷酸硫胺素的定量确定了乳腺癌细胞系中硫胺素转运和游离硫胺素水平的明显提高。总体而言，这些发现表明乳腺癌细胞的适应性反应可增加硫胺素的细胞利用率

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