Determine the effect of p53 on chemosensitivity.
Determine the effect of p53 on chemosensitivity.
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DOI：
10.1007/978-1-62703-236-0_9
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Manfredi JJ
中科院分区：
文献类型：
--
作者：
Senturk E;Manfredi JJ
p53 肿瘤抑制蛋白在介导细胞对各种应激的反应中发挥着核心作用。 p53 信号传导的激活将触发正常细胞的细胞周期停滞或凋亡，具体取决于细胞类型和遗传背景等因素。细胞规避这些 p53 导向结果中的任何一个的能力会导致不适当的增殖，从而导致癌症的发展。因此，肿瘤经常逃避细胞凋亡途径以应对细胞应激。然而，尽管具有这一标志性特征，DNA 损伤剂仍具有显着的肿瘤细胞毒性。用 DNA 损伤药物治疗的肿瘤除了可能最终导致消退的细胞凋亡之外，通常还会经历其他形式的细胞死亡，例如衰老或有丝分裂灾难。虽然本身不是患者化疗反应的预测因子，但肿瘤衍生细胞中的 p53 状态通常是这些药物促进的死亡途径的决定因素。使用细胞周期分析、phopsho-H3Ser10 免疫印迹和膜联蛋白 V 检测等工具可以轻松了解 DNA 损伤剂的细胞毒性作用。
The p53 tumor suppressor protein plays a central role in mediating the cellular response to a variety of stresses. Activation of p53 signaling will trigger cell cycle arrest or apoptosis in normal cells, depending on such factors as cell type and genetic context. The ability of a cell to circumvent either of these p53-directed outcomes leads to inappropriate proliferation, thereby contributing to the development of cancer. As such, tumors frequently escape the apoptotic pathway in response to cell stress. DNA-damaging agents, however, achieve significant tumor cytotoxicity in spite of this hallmark characteristic. Tumors treated with DNA-damaging drugs often undergo alternate forms of cell death, such as senescence or mitotic catastrophe, in addition to apoptosis that may ultimately lead to regression. Although not a predictor of chemotherapy response in patients per se, p53 status in tumor-derived cells is frequently a determinant of the death pathway promoted by these agents. The cytotoxic effects of DNA-damaging agents can be readily appreciated using such tools as cell cycle analysis, phopsho-H3Ser10 immunoblotting, and annexin V detection.