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极光激酶A在皮肤T细胞淋巴瘤中上调,是一个潜在的治疗靶点。

Aurora Kinase A Is Upregulated in Cutaneous T-Cell Lymphoma and Represents a Potential Therapeutic Target.

作者信息

Humme Daniel, Haider Ahmed, Möbs Markus, Mitsui Hiroshi, Suárez-Fariñas Mayte, Ohmatsu Hanako, Isabell Geilen Cyprienne, Eberle Jürgen, Krueger James G, Beyer Marc, Hummel Michael, Anagnostopoulos Ioannis, Sterry Wolfram, Assaf Chalid

机构信息

Department of Dermatology and Allergy, Skin Cancer Center Charité, Charité - Universitätsmedizin Berlin, Berlin, Germany.

Department of Dermatology and Allergy, Skin Cancer Center Charité, Charité - Universitätsmedizin Berlin, Berlin, Germany; These authors contributed equally to this work.

出版信息

J Invest Dermatol. 2015 Sep;135(9):2292-2300. doi: 10.1038/jid.2015.139. Epub 2015 Apr 7.

Abstract

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.

摘要

皮肤T细胞淋巴瘤(CTCL)是一组异质性非霍奇金淋巴瘤,其特征是晚期预后较差。尽管在鉴定皮肤淋巴瘤发病机制中涉及的新基因和通路方面取得了重大进展,但这些发现的治疗价值仍有待证实。在此,我们通过基因表达阵列证明,极光激酶A是CTCL中丝氨酸/苏氨酸激酶高度过表达的基因之一。在CTCL细胞系和原发性患者样本中,通过定量逆转录酶PCR、蛋白质印迹和免疫组织化学证实了这一发现。此外,用特异性极光激酶A抑制剂治疗可通过诱导CTCL细胞系在G2期细胞周期停滞以及凋亡来阻断细胞增殖。这些数据为使用极光激酶A抑制作为CTCL的治疗方式提供了有前景的理论依据。

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