Histone H1 phosphorylation in breast cancer.
Histone H1 phosphorylation in breast cancer.
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DOI：
10.1021/pr401248f
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发表时间：
2014-05-02
影响因子：
4.4
通讯作者：
Freitas, Michael A.
中科院分区：
文献类型：
--
作者：
Harshman, Sean W.;Hoover, Michael E.;Huang, Chengsi;Branson, Owen E.;Chaney, Sarah B.;Cheney, Carolyn M.;Rosol, Thomas J.;Shapiro, Charles L.;Wysocki, Vicki H.;Huebner, Kay;Freitas, Michael A.
乳腺癌是妇女癌症相关死亡的第二大原因。需要新的乳腺癌临床生物标志物来进一步预测预后和治疗反应。在这篇文章中，LC-MS组蛋白H1磷酸化的配置文件建立了三个不同的乳腺癌细胞系。结果表明，H1磷酸化的程度可以区分不同的细胞系。对来自转移性细胞系MDA-MB-231的组蛋白H1进行化学衍生化和LC-MS/MS分析。结果表明，在组蛋白H1.2和组蛋白H1.4上都发现了苏氨酸146的磷酸化。然后用细胞外刺激物、雌二醇或激酶抑制剂LY 294002处理细胞系，以监测组蛋白H1磷酸化的变化。这些数据表明，组蛋白H1磷酸化可以增加和减少响应细胞外刺激。最后，对原代乳腺组织进行组蛋白H1在苏氨酸146处的磷酸化染色。在肿瘤分级和亚型之间观察到不同的染色模式，其中pT 146标记与肿瘤分级相关。这些结果确立了组蛋白H1在苏氨酸146处磷酸化作为乳腺癌临床生物标志物的可能性。
Breast cancer is the second leading cause of cancer-related deaths in women. The need for new clinical biomarkers in breast cancer is necessary to further predict prognosis and therapeutic response. In this article, the LC-MS histone H1 phosphorylation profiles were established for three distinct breast cancer cell lines. The results show that the extent of H1 phosphorylation can distinguish between the different cell lines. The histone H1 from the metastatic cell line, MDA-MB-231, was subjected to chemical derivitization and LC-MS/MS analysis. The results suggest that the phosphorylation at threonine 146 is found on both histone H1.2 and histone H1.4. Cell lines were then treated with an extracellular stimulus, estradiol or kinase inhibitor LY294002, to monitor changes in histone H1 phosphorylation. The data show that histone H1 phosphorylation can increase and decrease in response to extracellular stimuli. Finally, primary breast tissues were stained for the histone H1 phosphorylation at threonine 146. Variable staining patterns across tumor grades and subtypes were observed with pT146 labeling correlating with tumor grade. These results establish the potential for histone H1 phosphorylation at threonine 146 as a clinical biomarker in breast cancer.
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影响因子：
14.9
作者：
Harshman SW;Young NL;Parthun MR;Freitas MA
通讯作者：
Freitas MA
影响因子：
82.9
作者：
Majewski, Ian J.;Bernards, Rene
通讯作者：
Bernards, Rene
影响因子：
14.8
作者：
Garcia, Benjamin A.;Mollah, Sahana;Hunt, Donald F.
通讯作者：
Hunt, Donald F.
影响因子：
4.4
作者：
Garcia, BA;Busby, SA;Hunt, DF
通讯作者：
Hunt, DF
影响因子：
7
作者：
Garcia, Benjamin A.;Joshi, Swati;Hunt, Donald F.
通讯作者：
Hunt, Donald F.