Expression analysis and molecular targeting of cyclin-dependent kinases in advanced melanoma Functional analysis and molecular targeting of cyclin-dependent kinase family members in advanced melanoma
Expression analysis and molecular targeting of cyclin-dependent kinases in advanced melanoma Functional analysis and molecular targeting of cyclin-dependent kinase family members in advanced melanoma
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DOI：
10.4161/cc.10.6.15079
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发表时间：
2011-03-15
期刊：
影响因子：
4.3
通讯作者：
Becker, Dorothea
中科院分区：
文献类型：
--
作者：
Abdullah, Christopher;Wang, Xiaolei;Becker, Dorothea
黑色素瘤研究的一个主要焦点仍然是寻找可能是原发性和转移性黑色素瘤分子治疗的合适靶点的基因/蛋白质。与这一努力相一致，本文所述研究的目的是确定干扰细胞周期进程，特别是选定的细胞周期蛋白依赖性激酶的表达和功能是否会损害晚期黑色素瘤的生物学特征。我们提供的数据表明，与痣和原位黑色素瘤不同，原发性和转移性黑色素瘤表达高水平的CDK 2、CDK 1和CDK 5。此外，我们提出了体外和临床前体内研究的结果，这些研究表明，用选择性阻断CDK 2，CDK 5，CDK 1和CDK 9功能的小分子细胞周期蛋白依赖性激酶抑制剂治疗，不仅可以抑制黑色素瘤细胞增殖和黑色素瘤细胞凋亡，还可以损害人黑色素瘤异种移植物的生长。
A major focus of melanoma research continues to be the search for genes/proteins that may be suitable targets for molecular therapy of primary and metastatic melanoma. In line with this effort, the objective of the study presented herein was to determine whether interfering with cell cycle progression and in particular, the expression and function of select cyclin-dependent kinases, would impair the biological features of advanced melanoma. We provide data, which document that unlike nevi and melanoma in situ, primary and metastatic melanomas express high levels of CDK2, CDK1, and CDK5. Furthermore, we present the results of in vitro and preclinical in vivo studies, which demonstrate that treatment with a small-molecule cyclin-dependent kinase inhibitor that selectively blocks the function of CDK2, CDK5, CDK1 and CDK9, leads not only to inhibition of melanoma cell proliferation and apoptosis of melanoma cells, but also impairs the growth of human melanoma xenografts.