晚期黑色素瘤中极光激酶A和B的功能分析及分子靶向研究
Functional analysis and molecular targeting of aurora kinases a and B in advanced melanoma.
作者信息
Wang Xiaolei, Moschos Stergios J, Becker Dorothea
机构信息
Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA.
出版信息
Genes Cancer. 2010 Sep;1(9):952-63. doi: 10.1177/1947601910388936.
Abstract
Over the past few years, high-throughput analyses have provided important novel insights into molecular pathways that play a crucial role in the progression from early to advanced melanoma, and at the same time, they have led to the identification of genes that as part of melanoma progression are upregulated in advanced melanoma. In the present study, we provide evidence that Aurora kinases A and B, 2 key regulators of M phase progression, are upregulated to high levels with progression from melanoma in situ to primary and metastatic melanoma and that inhibiting the expression of these 2 genes by RNA interference or blocking their function with an Aurora kinase-specific small-molecule inhibitor severely impairs melanoma cell proliferation and cell cycle progression and induces melanoma cell apoptosis. In addition, we present the results of systemic treatment of human melanoma xenografts with an Aurora kinase small-molecule inhibitor as well as Aurora kinase targeting vectors.
摘要
在过去几年中，高通量分析为在从早期到晚期黑色素瘤进展过程中起关键作用的分子途径提供了重要的新见解，同时，这些分析还导致了一些基因的鉴定，这些基因作为黑色素瘤进展的一部分在晚期黑色素瘤中上调。在本研究中，我们提供证据表明，Aurora激酶A和B这两个M期进展的关键调节因子，随着黑色素瘤从原位癌进展到原发性和转移性黑色素瘤，其表达上调至高水平，并且通过RNA干扰抑制这两个基因的表达或用Aurora激酶特异性小分子抑制剂阻断其功能会严重损害黑色素瘤细胞增殖和细胞周期进程，并诱导黑色素瘤细胞凋亡。此外，我们还展示了用Aurora激酶小分子抑制剂以及靶向Aurora激酶的载体对人黑色素瘤异种移植瘤进行全身治疗的结果。
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