Targeted Proteomic Analysis Revealed Kinome Reprogramming during Acquisition of Radioresistance in Breast Cancer Cells.

Targeted Proteomic Analysis Revealed Kinome Reprogramming during Acquisition of Radioresistance in Breast Cancer Cells.
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靶向蛋白质组学分析表明,在乳腺癌细胞中采集放射线抗性期间的Kinome重编程。

DOI:
10.1021/acs.jproteome.1c00075
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发表时间:
2021-05-07
影响因子:
4.4
通讯作者:
Wang Y
Wang Y
中科院分区:
生物学2区
文献类型:
--
作者:
Miao W;Bade D;Wang Y

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放射治疗是乳腺癌早期治疗的主要手段。尽管乳腺癌在治疗上有很高的疗效,但放射抵抗和肿瘤复发是乳腺癌放射治疗的主要障碍。为此,采用细胞培养中氨基酸稳定同位素标记(SILAC)结合平行反应监测(PRM)的靶向定量蛋白质组学方法,检测了乳腺癌MCF-7和MDA-MB-231细胞及其相应的辐射抗性C6和C5细胞株的蛋白表达差异。我们分别对C5/MDA-MB-231和C6/MCF-7乳腺癌细胞中300和281个激酶的相对蛋白表达水平进行了定量。我们还发现,TAF9是一种差异表达的激酶,它可以增强乳腺癌细胞的辐射抗性。此外,基因表达的相关性分析表明,TAF9的S在上调辐射抗性相关基因的表达方面发挥了作用。总体而言,我们的研究发现了大量差异表达的激酶伴随着辐射抵抗的获得,并揭示了TAF9在促进乳腺癌辐射抵抗中的作用。
Radiotherapy constitutes a major therapeutic modality for early management of breast cancer. Despite the high efficacy in treating breast cancer (BC), radiation resistance and tumor recurrence are major hurdles in breast cancer radiotherapy. Herein, stable isotope labeling by amino acids in cell culture (SILAC) was employed, along with the parallel-reaction monitoring (PRM)-based targeted quantitative proteomic method, to examine the differences in kinase protein expression in MCF-7 and MDA-MB-231 breast cancer cells and their corresponding radioresistant C6 and C5 clones. We quantified the relative protein expression levels of 300 and 281 kinases in C5/MDA-MB-231 and C6/MCF-7 pairs of breast cancer cells, respectively. We also showed that TAF9, which was one of the differentially expressed kinases, enhances radiation resistance in breast cancer cells. Moreover, a correlation analysis of gene expression suggested TAF9’s role in upregulating the expression of genes involved with radioresistance. Overall, our study uncovered a large number of differentially expressed kinases accompanied with the acquisition of radioresistance and revealed a role of TAF9 in promoting radioresistance in breast cancer.
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