Behera Rajendra Kumar, Nayak Rabindranath
Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India.
Cancer Invest. 2009 Jun;27(5):561-7. doi: 10.1080/07357900802620802.
5-Fluorouracil (5-FU) is one of the most widely used drugs for treatment of cancers, including breast cancer that exhibits its anticancer activity by inhibiting DNA synthesis and also incorporated into DNA and RNA. The objective of this investigation was to find out the total nucleotide metabolism genes regulated by 5-FU in breast cancer cell line. The breast cancer cell line MCF-7 was treated with the drug 5-FU. To analyze the expression of genes, we have conducted the experiment using 1.7 k and 19k human microarray slide and confirmed the expression of genes by semiquantitative reverse transcription-polymerase chain reaction. The expression of 44 genes involved in the nucleotide metabolism pathway was quantified. Of these 44 genes analyzed, transcription of 6 genes were upregulated and 9 genes were downregulated. Earlier studies revealed that the transcription of genes for key enzymes like thymidylate synthase, thymidine kinase, and dihydropyrimidine dehydrogenase are regulated by 5-FU. This study identified some novel genes like thioredoxin reductase, ectonucleotide triphosphate dephosphorylase, and CTP synthase are regulated by 5-FU. The data also reveal large-scale perturbation in transcription of genes not involved directly in the known mechanism of action of 5-FU.
5-氟尿嘧啶（5-FU）是治疗癌症最常用的药物之一，包括乳腺癌。它通过抑制DNA合成以及掺入DNA和RNA来发挥抗癌活性。本研究的目的是找出5-FU在乳腺癌细胞系中调控的总核苷酸代谢基因。用药物5-FU处理乳腺癌细胞系MCF-7。为了分析基因的表达，我们使用1.7k和19k人类微阵列玻片进行了实验，并通过半定量逆转录-聚合酶链反应确认了基因的表达。对参与核苷酸代谢途径的44个基因的表达进行了定量。在分析的这44个基因中，有6个基因的转录上调，9个基因的转录下调。早期研究表明，胸苷酸合成酶、胸苷激酶和二氢嘧啶脱氢酶等关键酶的基因转录受5-FU调控。本研究发现硫氧还蛋白还原酶、外核苷酸三磷酸二磷酸酶和CTP合成酶等一些新基因受5-FU调控。数据还显示，未直接参与5-FU已知作用机制的基因转录存在大规模扰动。
