Apoptosis-related gene expression after hyperthermia in human tongue squamous cell carcinoma cells harboring wild-type or mutated-type p53.
Apoptosis-related gene expression after hyperthermia in human tongue squamous cell carcinoma cells harboring wild-type or mutated-type p53.
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DOI：
10.1016/j.canlet.2003.07.005
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发表时间：
2004-02
期刊：
影响因子：
9.7
通讯作者：
J. Yasumoto;T. Kirita;A. Takahashi;K. Ohnishi;Y. Imai;K. Yuki;T. Ohnishi
中科院分区：
文献类型：
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作者：
J. Yasumoto;T. Kirita;A. Takahashi;K. Ohnishi;Y. Imai;K. Yuki;T. Ohnishi
热疗对人类头颈部癌症的治疗很有用，因为与深层器官相比，热疗进行体温调节相对容易。在这项研究中，我们将注意力集中在P53作为热疗癌症治疗的预测指标上。我们使用了两种人鳞状细胞癌(SAS)细胞系，除了P53蛋白外，它们的功能背景都相同。用DNA芯片检测热处理后细胞的热敏感性、细胞凋亡率及相关基因的表达。SAS/neo(野生型p53；wtp53)细胞对热敏感，且wtp53细胞对Caspase-3活性和细胞凋亡的诱导作用明显高于SAS/mp53(突变型p53；mp53)细胞。P5 3细胞中IL-12Rβ1基因表达下调，而促进凋亡基因caspase9、CD30和CD40的表达不依赖于p5 3。提示IL-12相关基因可抑制热诱导的mP53细胞凋亡。这些发现强烈表明，P53状态是一种有用的预测指标，可用于预测热疗的有效性。
Hyperthermia is useful for the treatment of human head and neck cancer, as it is relatively easy to perform thermoregulation when compared with deep organs. In this study, we focused attention on the p53 as a predictive indicator of hyperthermic cancer therapy. We used two kinds of cell lines of a human squamous cell carcinoma (SAS) with identical backgrounds of function except for the p53 protein. We assayed the heat sensitivity, frequency of apoptosis, and apoptosis-related gene expression after heat treatment using DNA array. The SAS/neo (wild-type p53; wtp53) cells were sensitive to heat, and the induction of Caspase-3 activation and apoptosis in the wtp53 cells was clearly high compared with the SAS/mp53 (mutated p53; mp53) cells. The gene expression of apoptosis suppressive-genes such as IL-12 p35 decreased in the wtp53 cells, and IL-12 R β1 increased in the mp53 cells, though apoptosis-promotive genes of Caspase-9, CD30 and CD40 were induced p53-independently by hyperthermia. It is suggested that heat-induced apoptosis was suppressed by IL-12-related genes in the mp53 cells. These findings strongly imply that p53 status is a useful candidate for a predictive indicator of the effectiveness in hyperthermic therapy.