KDM4C Activity Modulates Cell Proliferation and Chromosome Segregation in Triple-Negative Breast Cancer.
KDM4C Activity Modulates Cell Proliferation and Chromosome Segregation in Triple-Negative Breast Cancer.
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DOI：
10.4137/bcbcr.s40182
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Lizcano F
中科院分区：
文献类型：
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作者：
Garcia J;Lizcano F
含有jumonji的结构域蛋白KDM4C是一种与几种人类癌症发展相关的组蛋白去甲基化酶。然而，其在肿瘤谱系生存能力中的具体功能尚未确定。本研究利用特异性去甲基化酶抑制剂研究了KDM4C活性在三种三阴性乳腺癌细胞系细胞增殖和染色体分离中的重要性。免疫荧光分析表明，KDM4C被招募到有丝分裂染色体上，其活性的调节增加了有丝分裂分离错误的数量。然而，3-（4,5-二甲基噻唑-2-基）-2,5-二苯基溴化四唑（MTT）细胞增殖试验表明，去甲基化酶活性是细胞生存所必需的。这些结果表明，KDM4C的组蛋白去甲基化酶活性对于乳腺癌的进展至关重要，因为它在维持染色体稳定性和细胞生长方面发挥着重要作用，因此突出了它作为潜在的治疗靶点。
The Jumonji-containing domain protein, KDM4C, is a histone demethylase associated with the development of several forms of human cancer. However, its specific function in the viability of tumoral lineages is yet to be determined. This work investigates the importance of KDM4C activity in cell proliferation and chromosome segregation of three triple-negative breast cancer cell lines using a specific demethylase inhibitor. Immunofluorescence assays show that KDM4C is recruited to mitotic chromosomes and that the modulation of its activity increases the number of mitotic segregation errors. However, 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) cell proliferation assays demonstrate that the demethylase activity is required for cell viability. These results suggest that the histone demethylase activity of KDM4C is essential for breast cancer progression given its role in the maintenance of chromosomal stability and cell growth, thus highlighting it as a potential therapeutic target.