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ATM-mediated Mad1 Serine 214 phosphorylation regulates Mad1 dimerization and the spindle assembly checkpoint.ATM 介导的 Mad1 丝氨酸 214 磷酸化调节 Mad1 二聚化和纺锤体组装检查点。
Carcinogenesis. 2014 Sep;35(9):2007-13. doi: 10.1093/carcin/bgu087. Epub 2014 Apr 11.
2
Estrogen receptor α regulates ATM Expression through miRNAs in breast cancer.雌激素受体 α 通过 miRNA 在乳腺癌中调控 ATM 的表达。
Clin Cancer Res. 2013 Sep 15;19(18):4994-5002. doi: 10.1158/1078-0432.CCR-12-3700. Epub 2013 Jul 15.
3
Activation of the ATM-Snail pathway promotes breast cancer metastasis.ATM-Snail 通路的激活促进乳腺癌转移。
J Mol Cell Biol. 2012 Oct;4(5):304-15. doi: 10.1093/jmcb/mjs048. Epub 2012 Aug 24.
4
Aurora B kinase phosphorylates and instigates degradation of p53.极光激酶 B 使 p53 磷酸化并促使其降解。
Proc Natl Acad Sci U S A. 2012 Jun 12;109(24):E1513-22. doi: 10.1073/pnas.1110287109. Epub 2012 May 18.
5
Aurora-B mediated ATM serine 1403 phosphorylation is required for mitotic ATM activation and the spindle checkpoint.极光激酶 B 介导的 ATM 丝氨酸 1403 磷酸化对于有丝分裂期 ATM 的激活和纺锤体检验点至关重要。
Mol Cell. 2011 Nov 18;44(4):597-608. doi: 10.1016/j.molcel.2011.09.016.
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The kinetochore protein Bub1 participates in the DNA damage response.着丝粒蛋白 Bub1 参与 DNA 损伤反应。
DNA Repair (Amst). 2012 Feb 1;11(2):185-91. doi: 10.1016/j.dnarep.2011.10.018. Epub 2011 Nov 9.
7
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8
Expression of Aurora A (but not Aurora B) is predictive of survival in breast cancer.极光激酶A(而非极光激酶B)的表达可预测乳腺癌患者的生存率。
Clin Cancer Res. 2008 Jul 15;14(14):4455-62. doi: 10.1158/1078-0432.CCR-07-5268.
9
Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy.测量残余乳腺癌负担以预测新辅助化疗后的生存率。
J Clin Oncol. 2007 Oct 1;25(28):4414-22. doi: 10.1200/JCO.2007.10.6823. Epub 2007 Sep 4.
10
Aurora-kinase inhibitors as anticancer agents.极光激酶抑制剂作为抗癌药物。
Nat Rev Cancer. 2004 Dec;4(12):927-36. doi: 10.1038/nrc1502.

Aurora B表达升高导致乳腺癌的化疗耐药和预后不良。

Elevated Aurora B expression contributes to chemoresistance and poor prognosis in breast cancer.

作者信息

Zhang Yiqian, Jiang Chunling, Li Huilan, Lv Feng, Li Xiaoyan, Qian Xiaolong, Fu Li, Xu Bo, Guo Xiaojing

机构信息

Department of Breast Pathology and Lab, Key Laboratory of Breast Cancer Prevention and Therapy, National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute and Hospital Tianjin 300060, China.

Department of Oncology, Southern Research Institute Birmingham, AL 35205.

出版信息

Int J Clin Exp Pathol. 2015 Jan 1;8(1):751-7. eCollection 2015.

PMID:25755770
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4348845/
Abstract

Aurora-B is a major kinase responsible for appropriate mitotic progression. Elevated expression of Aurora-B has been frequently associated with several types of cancer, including breast cancer. However, it is not clear whether the alteration contributes to tumor responses to therapies and prognosis. In this study, we conducted immunohistochemistry using antibodies against Aurora-B, S1981p-ATM, Ki67, and p53 in paraffin-embedded tumor tissues from 312 invasive breast cancer patients. The correlation between disease-free-survival (DFS) and Aurora-B expression was analyzed using the Kaplan-Meier method and log-rank test. A Cox proportional hazards regression analysis was used to determine whether Aurora-B was an independent prognostic factor for breast cancer. We found that Aurora-B expression was correlated with the proliferation index (P < 0.001) and p53 expression (P = 0.014) in breast cancer tissues. Further we found that Aurora-B expression was associated with lymph node metastasis (P = 0.002) and histological grade (P = 0.001). Multivariate analyses indicated that elevated Aurora-B expression predicted a poor survival. In a subgroup of patients that received neoadjuvant chemotherapy, we found that elevated Aurora-B contributed to chemoresistance (P = 0.011). In conclusion, elevated Aurora-B expression in breast cancer patients contributes to chemoresistance and predicts poor prognosis.

摘要

极光激酶B是一种主要的激酶,负责有丝分裂的正常进行。极光激酶B的表达升高常与包括乳腺癌在内的多种癌症相关。然而,尚不清楚这种改变是否会影响肿瘤对治疗的反应及预后。在本研究中,我们对312例浸润性乳腺癌患者石蜡包埋的肿瘤组织进行免疫组化,检测极光激酶B、S1981p-ATM、Ki67和p53。采用Kaplan-Meier法和对数秩检验分析无病生存期(DFS)与极光激酶B表达之间的相关性。使用Cox比例风险回归分析确定极光激酶B是否为乳腺癌的独立预后因素。我们发现,乳腺癌组织中极光激酶B的表达与增殖指数(P < 0.001)和p53表达(P = 0.014)相关。进一步发现,极光激酶B的表达与淋巴结转移(P = 0.002)和组织学分级(P = 0.001)相关。多因素分析表明,极光激酶B表达升高预示着生存不良。在接受新辅助化疗的患者亚组中,我们发现极光激酶B表达升高与化疗耐药相关(P = 0.011)。总之,乳腺癌患者中极光激酶B表达升高与化疗耐药相关,并预示预后不良。