mRNA expression levels of E2F transcription factors correlate with dihydrofolate reductase, reduced folate carrier, and thymidylate synthase mRNA expression in osteosarcoma.
mRNA expression levels of E2F transcription factors correlate with dihydrofolate reductase, reduced folate carrier, and thymidylate synthase mRNA expression in osteosarcoma.
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发表时间：
2003-06
影响因子：
5.7
通讯作者：
R. Sowers;J. Toguchida;J. Qin;P. Meyers;J. Healey;A. Huvos;D. Banerjee;J. Bertino;R. Gorlick
中科院分区：
文献类型：
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作者：
R. Sowers;J. Toguchida;J. Qin;P. Meyers;J. Healey;A. Huvos;D. Banerjee;J. Bertino;R. Gorlick
先前的研究表明，在骨肉瘤（OS）中，还原叶酸载体（RFC）表达减少和二氢叶酸还原酶（DHFR）表达增加分别与内在和获得性甲氨蝶呤耐药相关。在结直肠癌中还发现，E2F-1 表达与胸苷酸合酶 (TS) 相关，并且在较小程度上与 DHFR 表达相关。为了开始研究 OS 样品中 DHFR 和 RFC 表达的调节，测量了 OS 肿瘤样品中 E2F-1 和 E2F-4 的 mRNA 表达，并与 DHFR、RFC 和 TS mRNA 表达相关。使用荧光定量实时 PCR，研究了 112 名人类 OS 患者样本的潜在 E2F-1/E2F-4:DHFR、E2F-1/E2F-4:RFC 和 E2F-1/E2F-4:TS 相关性。每个基因的表达范围如下：DHFR，0.02-33.13（中位数= 0.20）； RFC，0.02-229.13（中位数 = 1.91）； TS，0.01-9.99（中位数 = 0.15）； E2F-1，0.05-69.07（中位数 = 0.52）；和 E2F-4，0.24-52.35（中位数 = 1.45）。 E2F-1:DHFR、E2F-1:RFC、E2F-1:TS、E2F-4:DHFR、E2F-4:RFC 和 E2F-4:TS 的 Spearman 相关系数 (r(s)) 经计算分别为 0.53、0.63、0.60、0.41、0.58 和 0.33（P < 0.001）。根据该数据，E2F-1/E2F-4 与 DHFR、RFC 和 TS 之间存在中等相关性。这些结果表明E2F-1/E2F-4可能在RFC表达的调节中发挥作用，这是以前未报道过的。 E2F 转录因子还与 OS 样本中的 DHFR 和 TS 表达相关，表明可能与甲氨蝶呤耐药有关。尽管 E2F mRNA 水平与 DHFR、RFC 和 TS mRNA 表达相关，但仍需要进行额外的实验来确定这些转录因子的直接影响，并鉴定可能影响这种关系的其他蛋白质。
Previous studies have shown that decreased expression of the reduced folate carrier (RFC) and increased expression of dihydrofolate reductase (DHFR) are associated with intrinsic and acquired methotrexate resistance, respectively, in osteosarcoma (OS). It has also been shown in colorectal cancer that E2F-1 expression correlates with thymidylate synthase (TS) and, to a lesser extent, DHFR expression. To begin to investigate the regulation of DHFR and RFC expression in OS samples, mRNA expression of E2F-1 and E2F-4 were measured in OS tumor samples and related to DHFR, RFC, and TS mRNA expression. Using fluorescent quantitative real-time PCR, 112 human OS patient samples were investigated for potential E2F-1/E2F-4:DHFR, E2F-1/E2F-4:RFC, and E2F-1/E2F-4:TS correlations. The expression ranges for each gene are as follows: DHFR, 0.02-33.13 (median = 0.20); RFC, 0.02-229.13 (median = 1.91); TS, 0.01-9.99 (median = 0.15); E2F-1, 0.05-69.07 (median = 0.52); and E2F-4, 0.24-52.35 (median = 1.45). Spearman correlation coefficients (r(s)) for E2F-1:DHFR, E2F-1:RFC, E2F-1:TS, E2F-4:DHFR, E2F-4:RFC, and E2F-4:TS were calculated to be 0.53, 0.63, 0.60, 0.41, 0.58, and 0.33, respectively (P < 0.001). On the basis of this data, moderate correlations exist between E2F-1/E2F-4 and DHFR, RFC, and TS. These results suggest E2F-1/E2F-4 may play a role in the regulation of RFC expression, which has not been reported previously. The E2F transcription factors are also related to DHFR and TS expression in OS samples, suggesting a possible involvement in methotrexate resistance. Although E2F mRNA levels correlate with DHFR, RFC, and TS mRNA expression, additional experiments are necessary to determine the direct effects of these transcription factors and identify other proteins that may influence this relationship.