Tissue microarray analysis of eIF4E and its downstream effector proteins in human breast cancer.

Tissue microarray analysis of eIF4E and its downstream effector proteins in human breast cancer.
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DOI:
10.1186/1756-9966-28-5
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发表时间:
2009-01-09
期刊:
Journal of experimental & clinical cancer research : CR
影响因子:
--
通讯作者:
Li BD
Li BD
中科院分区:
其他
文献类型:
--
作者:
Kleiner HE;Krishnan P;Tubbs J;Smith M;Meschonat C;Shi R;Lowery-Nordberg M;Adegboyega P;Unger M;Cardelli J;Chu Q;Mathis JM;Clifford J;De Benedetti A;Li BD

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真核起始因子4E (eIF4E)在许多癌症中升高,是乳腺癌的预后指标。许多促肿瘤蛋白可通过eIF4E选择性翻译,包括c-Myc、cyclin D1、鸟氨酸脱羧酶(ODC)、血管内皮生长因子(VEGF)和tousled样激酶1B (TLK1B)。然而,人类乳腺癌中这些因素的western blot分析受到新鲜冷冻组织的可用性和所需的多次检测的劳动密集型性质的限制。我们的目的是验证用组织微阵列(TMA)格式排列的福尔马林固定石蜡包埋组织是否比使用新鲜冷冻组织和western blot检测多个下游基因产物更有效。对乳腺肿瘤TMAs进行免疫组织化学染色,并用ARIOL成像系统进行定量。在tma中,eIF4E水平与c-Myc、cyclin D1、TLK1B、VEGF和ODC密切相关。Western blot比较eIF4E与TLK1B与免疫组化结果一致。与我们之前的western blot结果一致,eIF4E与节点状态、ER、PR或HER-2/neu无关。我们得出结论,TMA技术产生的结果与western blot技术相似,并且可以更有效和彻底地评估eIF4E下游的几种产品。
Eukaryotic initiation factor 4E (eIF4E) is elevated in many cancers and is a prognostic indicator in breast cancer. Many pro-tumorigenic proteins are selectively translated via eIF4E, including c-Myc, cyclin D1, ornithine decarboxylase (ODC), vascular endothelial growth factor (VEGF) and Tousled-like kinase 1B (TLK1B). However, western blot analysis of these factors in human breast cancer has been limited by the availability of fresh frozen tissue and the labor-intensive nature of the multiple assays required. Our goal was to validate whether formalin-fixed, paraffin-embedded tissues arranged in a tissue microarray (TMA) format would be more efficient than the use of fresh-frozen tissue and western blot to test multiple downstream gene products. Breast tumor TMAs were stained immunohistochemically and quantitated using the ARIOL imaging system. In the TMAs, eIF4E levels correlated strongly with c-Myc, cyclin D1, TLK1B, VEGF, and ODC. Western blot comparisons of eIF4E vs. TLK1B were consistent with the immunohistochemical results. Consistent with our previous western blot results, eIF4E did not correlate with node status, ER, PR, or HER-2/neu. We conclude that the TMA technique yields similar results as the western blot technique and can be more efficient and thorough in the evaluation of several products downstream of eIF4E.
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