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首页> 外文期刊>International Journal for Vitamin and Nutrition Research: Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung >Expression of oncogenes depends on biotin in human small cell lung cancer cells NCI-H69.
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Expression of oncogenes depends on biotin in human small cell lung cancer cells NCI-H69.

机译:癌基因的表达取决于生物素在人小细胞肺癌细胞NCI-H69中的表达。

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摘要

Oncogenes play important roles in cell proliferation and biotin status correlates with gene expression and proliferation rates in human cells. In this study we determined whether biotin supply affects biotin homeostasis, expression of oncogenes, and proliferation rates in NCI-H69 small cell lung cancer cells. NCI-H69 cells were cultured in media containing deficient (0.025 nmol/L), physiologic (0.25 nmol/L), or pharmacologic (10 nmol/L) concentrations of biotin for 3 weeks. Biotin concentrations in culture media correlated negatively with biotin transport rates, suggesting that cells responded to marginal biotin supply with increased expression of biotin transporters. Increased biotin uptake was not sufficient to prevent depletion of intracellular biotin in cells cultured in biotin-deficient medium, as judged by decreased activity of biotin-dependent propionyl-CoA carboxylase and decreased biotinylation of histones. The expression of oncogenes N-myc, c-myb, N-ras, and raf correlated with biotin supply in media: oncogene expression increased by up to 20% in cells cultured in pharmacologic medium compared to physiologic controls; oncogene expression decreased by up to 47% in cells cultured in deficient medium. This observation is consistent with a role for biotin in oncogene-dependent metabolic pathways. Cellular uptake of thymidine (marker for proliferation) was not affected by biotin supply, suggesting that effects of biotin-dependent expression of oncogenes on the growth of tumor cells are quantitatively minor. The clinical significance of effects of biotin supply on expression of oncogenes remains to be elaborated.
机译:癌基因在细胞增殖中起着重要作用,生物素状态与人类细胞中的基因表达和增殖速率相关。在这项研究中,我们确定了生物素供应是否会影响NCI-H69小细胞肺癌细胞中生物素的稳态,癌基因的表达以及增殖率。将NCI-H69细胞在含有不足浓度(0.025 nmol / L),生理浓度(0.25 nmol / L)或药物浓度(10 nmol / L)的生物素的培养基中培养3周。培养基中生物素浓度与生物素转运速率负相关,表明细胞对边缘生物素供应的反应随着生物素转运蛋白表达的增加而增加。由生物素依赖性丙酰辅酶A羧化酶活性降低和组蛋白生物素化降低所判断,增加的生物素摄取不足以防止在缺乏生物素的培养基中培养的细胞中细胞内生物素的消耗。癌基因N-myc,c-myb,N-ras和raf的表达与培养基中生物素的供应有关:与生理对照相比,在药理培养基中培养的细胞中,癌基因的表达增加了20%。在缺乏培养基中培养的细胞中,癌基因表达最多降低47%。该观察结果与生物素在癌基因依赖性代谢途径中的作用一致。胸腺嘧啶核苷的细胞摄取(增殖标志)不受生物素供应的影响,这表明生物素依赖性癌基因表达对肿瘤细胞生长的影响在数量上较小。生物素供应对癌基因表达的影响的临床意义尚待阐明。

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