Aurora Kinase A Is Upregulated in Cutaneous T-Cell Lymphoma and Represents a Potential Therapeutic Target
Aurora Kinase A Is Upregulated in Cutaneous T-Cell Lymphoma and Represents a Potential Therapeutic Target
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DOI：
10.1038/jid.2015.139
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发表时间：
2015-09-01
影响因子：
6.5
通讯作者：
Assaf, Chalid
中科院分区：
文献类型：
--
作者：
Humme, Daniel;Haider, Ahmed;Assaf, Chalid
皮肤T细胞淋巴瘤(CTCL)是一组异质性的非霍奇金淋巴瘤，其特征是晚期预后不良。尽管在识别与皮肤淋巴瘤发病相关的新基因和新途径方面取得了重大进展，但这些发现的治疗价值仍有待证实。在这里，我们通过基因表达阵列证明，极光激酶A是CTCL中丝/苏氨酸激酶的高表达基因之一。定量逆转录聚合酶链式反应、免疫印迹和免疫组织化学在CTCL细胞系和原发患者样本中证实了这一发现。此外，用特定的Aurora激酶A抑制剂处理通过诱导细胞周期停滞在G2期来阻止细胞增殖，以及抑制CTCL细胞系的凋亡。这些数据为使用Aurora激酶A抑制作为CTCL的一种治疗方式提供了一个有希望的理论基础。
Cutaneous T-cell lymphomas (CTCLs) form a heterogeneous group of non-Hodgkin's lymphomas characterized by only poor prognosis in advanced stage. Despite significant progress made in the identification of novel genes and pathways involved in the pathogenesis of cutaneous lymphoma, the therapeutic value of these findings has still to be proven. Here, we demonstrate by gene expression arrays that Aurora kinase A is one of the highly overexpressed genes of the serine/threonine kinase in CTCL. The finding was confirmed by quantitative reverse transcriptase-PCR, western blotting, and immunohistochemistry in CTCL cell lines and primary patient samples. Moreover, treatment with a specific Aurora kinase A inhibitor blocks cell proliferation by inducing cell cycle arrest in G2 phase, as well as apoptosis in CTCL cell lines. These data provide a promising rationale for using Aurora kinase A inhibition as a therapeutic modality of CTCL.