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首页> 外文期刊>International Journal of Molecular Sciences >Mirk/dyrk1B Kinase in Ovarian Cancer
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Mirk/dyrk1B Kinase in Ovarian Cancer

机译：Mirk / dyrk1B激酶在卵巢癌中的作用

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Mirk/dyrk1B kinase is expressed in about 75% of resected human ovarian cancers and in most ovarian cancer cell lines with amplification in the OVCAR3 line. Mirk (minibrain-related kinase) is a member of the Minibrain/dyrk family of related serine/threonine kinases. Mirk maintains cells in a quiescent state by stabilizing the CDK inhibitor p27 and by inducing the breakdown of cyclin D isoforms. Mirk also stabilizes the DREAM complex, which maintains G0 quiescence by sequestering transcription factors needed to enter cycle. By entering a quiescent state, tumor cells can resist the nutrient deficiencies, hypoxic and acidic conditions within the tumor mass. Mirk maintains the viability of quiescent ovarian cancer cells by reducing intracellular levels of reactive oxygen species. CDKN2A-negative ovarian cancer cells treated with a Mirk kinase inhibitor escaped G0/G1 quiescence, entered cycle with high ROS levels and underwent apoptosis. The ROS scavenger N-acetyl cysteine reduced the extent of cancer cell loss. In contrast, the Mirk kinase inhibitor slightly reduced the fraction of G0 quiescent diploid epithelial cells and fibroblasts, and the majority of the cells pushed into cycle accumulated in G2 + M. Apoptotic sub-G0/G1 cells were not detected. Thus, normal cells were spared because of their expression of CDK inhibitors that blocked unregulated cycling and Mirk kinase inhibitor-treated normal diploid cells were about as viable as untreated controls.
机译：Mirk / dyrk1B激酶在约75％切除的人类卵巢癌和大多数卵巢癌细胞系中表达，并在OVCAR3系中扩增。 Mirk（小脑相关激酶）是相关丝氨酸/苏氨酸激酶的Minibrain / dyrk家族的成员。 Mirk通过稳定CDK抑制剂p27并诱导细胞周期蛋白D同工型分解，使细胞保持静止状态。 Mirk还可以稳定DREAM复合物，该复合物通过隔离进入循环所需的转录因子来维持G0静止。通过进入静止状态，肿瘤细胞可以抵抗肿瘤块内的营养缺乏，低氧和酸性条件。 Mirk通过降低细胞内活性氧的含量来维持卵巢癌细胞的活力。用Mirk激酶抑制剂处理的CDKN2A阴性卵巢癌细胞逃脱了G0 / G1静止期，进入具有高ROS水平的周期并经历了凋亡。 ROS清除剂N-乙酰半胱氨酸减少了癌细胞损失的程度。相比之下，Mirk激酶抑制剂稍微降低了G0静态二倍体上皮细胞和成纤维细胞的比例，并且大部分进入G2 + M的细胞进入了循环。未检测到凋亡的亚G0 / G1细胞。因此，正常细胞得以幸免，因为它们表达的CDK抑制剂可阻断不受调节的循环，而Mirk激酶抑制剂处理的正常二倍体细胞的存活率与未处理的对照差不多。

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