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Differential levels of Alpha-1-inhibitor III, Immunoglobulin heavy chain variable region, and Hypertrophied skeletal muscle protein GTF3 in rat mammary tumorigenesis.
Biochimie ( IF 3.3 ) Pub Date : 2020-04-20 , DOI: 10.1016/j.biochi.2020.04.013 Ishfaq Ahmad Ganaie 1 , Md Zubbair Malik 2 , Samar Husain Naqvi 3 , Swatantra Kumar Jain 4 , Saima Wajid 1
Biochimie ( IF 3.3 ) Pub Date : 2020-04-20 , DOI: 10.1016/j.biochi.2020.04.013 Ishfaq Ahmad Ganaie 1 , Md Zubbair Malik 2 , Samar Husain Naqvi 3 , Swatantra Kumar Jain 4 , Saima Wajid 1
Affiliation
Early detection of breast cancer can be best facilitated by the development of precancerous markers. Serum proteins being the sensitive signatures, can be the ideal choice. We previously demonstrated the reduced levels of two serum proteins at a very early stage of tumorigenesis in a breast cancer model, developed in Wistar rats by 7,12-dimethylbenz[a]anthracene (DMBA) administration. Here we report the dysregulation of three more proteins in the serum collected at another early stage (15 weeks) of tumorigenesis in the same model. The proteins were identified (as Alpha-1-inhibitor III (Mug1), Immunoglobulin heavy chain variable region (IGHV), and Hypertrophied skeletal muscle protein GTF3) by MALDI-TOF MS after the screening and fingerprinting of serum samples by one-dimensional (1D) and two-dimensional (2D) electrophoresis respectively. Relative expression analysis of corresponding genes was also carried out, and the results were found as supporting the proteomic findings. In addition, the candidate proteins of the study and their corresponding ribonucleic acids (RNAs) were subjected to homology modelling and docking (using softwares like MODELLER, 3dRNA, Autodock4.0, and GROMACS etc), which revealed the binding sites for carcinogen (DMBA) and its nature of interaction with proteins and RNAs. Moreover, the network analysis by GeneMANIA unraveled the protein/gene functional network in which Mug1, IGHV, and GTF3 are involved. Based on the significant protein and gene expression alterations in early tumorigenesis, these proteins may prove very effective in search for biomarkers for the early detection of mammary cancer. Further, these proteins can also be tried as targets for chemotherapy.
中文翻译：
大鼠乳腺肿瘤发生过程中Alpha-1抑制剂III，免疫球蛋白重链可变区和肥大性骨骼肌蛋白GTF3的差异水平。
癌前标记物的发展可以最好地促进乳腺癌的早期发现。血清蛋白是敏感的特征，可以是理想的选择。我们先前证明了在乳腺癌模型的肿瘤发生的非常早期阶段，两种血清蛋白的含量降低，该模型在Wistar大鼠中通过7,12-二甲基苯并[a]蒽（DMBA）给药而开发。在这里，我们报告在同一模型中，在肿瘤发生的另一个早期阶段（15周）收集的血清中的另外三种蛋白质失调。在对血清样品进行一维筛查和指纹分析后，通过MALDI-TOF MS鉴定了这些蛋白（如Alpha-1-抑制剂III（Mug1），免疫球蛋白重链可变区（IGHV）和肥大性骨骼肌蛋白GTF3）。 1D）和二维（2D）电泳。还进行了相应基因的相对表达分析，结果被证明支持蛋白质组学研究。此外，对研究的候选蛋白及其相应的核糖核酸（RNA）进行了同源建模和对接（使用诸如MODELLER，3dRNA，Autodock4.0和GROMACS等软件），从而揭示了致癌物（DMBA）的结合位点。 ）及其与蛋白质和RNA相互作用的性质。此外，GeneMANIA进行的网络分析揭示了涉及Mug1，IGHV和GTF3的蛋白质/基因功能网络。基于早期肿瘤发生中显着的蛋白质和基因表达改变，这些蛋白质可能被证明在寻找生物标志物以早期发现乳腺癌中非常有效。进一步，
更新日期：2020-04-20
中文翻译：
大鼠乳腺肿瘤发生过程中Alpha-1抑制剂III，免疫球蛋白重链可变区和肥大性骨骼肌蛋白GTF3的差异水平。
癌前标记物的发展可以最好地促进乳腺癌的早期发现。血清蛋白是敏感的特征，可以是理想的选择。我们先前证明了在乳腺癌模型的肿瘤发生的非常早期阶段，两种血清蛋白的含量降低，该模型在Wistar大鼠中通过7,12-二甲基苯并[a]蒽（DMBA）给药而开发。在这里，我们报告在同一模型中，在肿瘤发生的另一个早期阶段（15周）收集的血清中的另外三种蛋白质失调。在对血清样品进行一维筛查和指纹分析后，通过MALDI-TOF MS鉴定了这些蛋白（如Alpha-1-抑制剂III（Mug1），免疫球蛋白重链可变区（IGHV）和肥大性骨骼肌蛋白GTF3）。 1D）和二维（2D）电泳。还进行了相应基因的相对表达分析，结果被证明支持蛋白质组学研究。此外，对研究的候选蛋白及其相应的核糖核酸（RNA）进行了同源建模和对接（使用诸如MODELLER，3dRNA，Autodock4.0和GROMACS等软件），从而揭示了致癌物（DMBA）的结合位点。 ）及其与蛋白质和RNA相互作用的性质。此外，GeneMANIA进行的网络分析揭示了涉及Mug1，IGHV和GTF3的蛋白质/基因功能网络。基于早期肿瘤发生中显着的蛋白质和基因表达改变，这些蛋白质可能被证明在寻找生物标志物以早期发现乳腺癌中非常有效。进一步，
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