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Dyrk1B过表达与乳腺癌生长及不良预后相关。

Dyrk1B overexpression is associated with breast cancer growth and a poor prognosis.

作者信息

Chen Yingying, Wang Shuo, He Zhixian, Sun Fulan, Huang Yeqing, Ni Qichao, Wang Hua, Wang Yingying, Cheng Chun

机构信息

Department of Immunology, Medical College, Nantong University, Nantong 226001, Jiangsu Province, People's Republic of China; Department of Oncology, Affiliated Hospital of Nantong University, Nantong 226001, China.

Department of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Nantong 226001, China.

出版信息

Hum Pathol. 2017 Aug;66:48-58. doi: 10.1016/j.humpath.2017.02.033. Epub 2017 May 26.

Abstract

Dyrk1B, also called minibrain-related kinase (Mirk), is a member of the dual-specificity tyrosine phosphorylation-regulated kinase (Dyrk)/minibrain family of dual-specificity protein kinases. It is a serine/threonine kinase involved in the regulation of tumor progression and cell proliferation. In this study, the role of Dyrk1B in breast cancer development was investigated. The expression of Dyrk1B was detected by Western blot and immunohistochemistry staining, both of which demonstrated that Dyrk1B was overexpressed in breast cancer tissues and cells. Statistical analysis showed that the extent of Dyrk1B expression was associated with multiple clinicopathologic factors, including tumor size, grade, estrogen receptor status, and Ki-67 expression, and that high expression predicted a poor prognosis. The growth of breast cancer cells was inhibited significantly after knockout of DYRK1B by small interfering RNA (siRNA). Moreover, FoxO1 could be phosphorylated by Dyrk1B, and then FoxO1 was shuttled from the cell nucleus into the cytoplasm, which might be the mechanism of Dyrk1B-mediated survival in breast cancer cells. The results suggest that Dyrk1B plays a key role in the progression of breast cancer and provides a new target for breast cancer therapy.

摘要

酪蛋白激酶1B(Dyrk1B),也称为小脑相关激酶(Mirk),是双特异性酪氨酸磷酸化调节激酶(Dyrk)/双特异性蛋白激酶小脑家族的成员。它是一种丝氨酸/苏氨酸激酶,参与肿瘤进展和细胞增殖的调节。在本研究中,研究了Dyrk1B在乳腺癌发生发展中的作用。通过蛋白质免疫印迹法和免疫组织化学染色检测Dyrk1B的表达,二者均表明Dyrk1B在乳腺癌组织和细胞中过表达。统计分析表明,Dyrk1B的表达程度与多种临床病理因素相关,包括肿瘤大小、分级、雌激素受体状态和Ki-67表达,且高表达预示着预后不良。通过小干扰RNA(siRNA)敲除DYRK1B后,乳腺癌细胞的生长受到显著抑制。此外,FoxO1可被Dyrk1B磷酸化,然后从细胞核穿梭至细胞质,这可能是Dyrk1B介导乳腺癌细胞存活的机制。结果表明,Dyrk1B在乳腺癌进展中起关键作用,并为乳腺癌治疗提供了新的靶点。

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