Combined analysis of eIF4E and 4E-binding protein expression predicts breast cancer survival and estimates eIF4E activity.
Combined analysis of eIF4E and 4E-binding protein expression predicts breast cancer survival and estimates eIF4E activity.
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DOI：
10.1038/sj.bjc.6605044
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发表时间：
2009-05-05
影响因子：
8.8
通讯作者：
Hughes, T. A.
中科院分区：
文献类型：
--
作者：
Coleman, L. J.;Peter, M. B.;Teall, T. J.;Brannan, R. A.;Hanby, A. M.;Honarpisheh, H.;Shaaban, A. M.;Smith, L.;Speirs, V.;Verghese, E. T.;McElwaine, J. N.;Hughes, T. A.
真核生物翻译起始因子4 E（eIF 4 E）表达的增加发生在许多癌症中，并且通过在转录后水平刺激癌症相关基因的表达而对致癌作用做出根本贡献。eIF 4 E水平可以预测预后，并且eIF 4 E是一个既定的治疗靶点，这一事实突出了这一关键作用。然而，eIF 4 E活性是eIF 4 E和eIF 4 E结合蛋白（4 E-BP）的表达水平和磷酸化状态的复杂函数。我们的假设是，这些途径组分的组合分析将允许深入了解eIF 4 E活性及其对癌症的影响。我们测定了424例乳腺肿瘤中eIF 4 E、4 E-BP 1、4 E-BP 2和磷酸化4 E-BP 1的表达水平，并进行了分析，以将这些联合收割机结合起来，并将产物与患者存活率联系起来，以估计eIF 4 E活性。我们表明，这种分析比单独的eIF 4 E提供了更好的预后见解。我们发现eIF 4 E和4 E-BP表达呈正相关，并且4 E-BP 2对癌症行为的影响比4 E-BP 1更强。最后，我们检查eIF 4 E，估计eIF 4 E活性，和磷酸化的4 E-BP 1作为eIF 4 E靶向治疗的潜在预测生物标志物，并表明每个决定不同患者组的选择。我们的结论是eIF 4 E对癌症生存的影响是由4 E-BPs大幅调制，并结合途径分析可以估计功能eIF 4 E。
Increased eukaryotic translation initiation factor 4E (eIF4E) expression occurs in many cancers, and makes fundamental contributions to carcinogenesis by stimulating the expression of cancer-related genes at post-transcriptional levels. This key role is highlighted by the facts that eIF4E levels can predict prognosis, and that eIF4E is an established therapeutic target. However, eIF4E activity is a complex function of expression levels and phosphorylation statuses of eIF4E and eIF4E-binding proteins (4E-BPs). Our hypothesis was that the combined analyses of these pathway components would allow insights into eIF4E activity and its influence on cancer. We have determined expression levels of eIF4E, 4E-BP1, 4E-BP2 and phosphorylated 4E-BP1 within 424 breast tumours, and have carried out analyses to combine these and relate the product to patient survival, in order to estimate eIF4E activity. We show that this analysis gives greater prognostic insights than that of eIF4E alone. We show that eIF4E and 4E-BP expression are positively associated, and that 4E-BP2 has a stronger influence on cancer behaviour than 4E-BP1. Finally, we examine eIF4E, estimated eIF4E activity, and phosphorylated 4E-BP1 as potential predictive biomarkers for eIF4E-targeted therapies, and show that each determines selection of different patient groups. We conclude that eIF4E's influence on cancer survival is modulated substantially by 4E-BPs, and that combined pathway analyses can estimate functional eIF4E.
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DOI：
10.1083/jcb.115.4.887
发表时间：
1991-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kozak M
通讯作者：
Kozak M
有效使用 PI3K 和 MEK 抑制剂治疗突变型 Kras G12D 和 PIK3CA H1047R 小鼠肺癌。
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
6.2
作者：
Castellvi, Josep;Garcia, Angel;Ramon y Cajal, Santiago
通讯作者：
Ramon y Cajal, Santiago
影响因子：
64.8
作者：
Richter, JD;Sonenberg, N
通讯作者：
Sonenberg, N
影响因子：
3.5
作者：
Pesole, G;Mignone, F;Liuni, S
通讯作者：
Liuni, S