Increased resistance of tumor cells to hyperthermia mediated by integrin-linked kinase.
Increased resistance of tumor cells to hyperthermia mediated by integrin-linked kinase.
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发表时间：
2003-03
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通讯作者：
Xiuwu Zhang;Yongping Li;Qian Huang;He Wang;B. Yan;M. Dewhirst;Chuan-Yuan Li
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作者：
Xiuwu Zhang;Yongping Li;Qian Huang;He Wang;B. Yan;M. Dewhirst;Chuan-Yuan Li
目的 整合素连接激酶 (ILK) 是一种丝氨酸-苏氨酸激酶，与锚定非依赖性生长和致瘤转化相关。先前的研究表明ILK的过度表达在几种类型的肿瘤中很常见，并且它参与应激下肿瘤细胞存活的调节。在这项研究中，我们检查了 ILK 表达对肿瘤细胞对热疗反应的影响。实验设计我们使用腺病毒介导的方法在前列腺癌细胞系中过度表达ILK基因，并检查其对热应激诱导的细胞死亡的影响。在过度表达 ILK 的细胞中评估克隆形成存活和细胞凋亡。此外，在同基因宿主中检查了体内形成肿瘤的能力。最后，通过确定多种信号转导途径的状态来检查ILK介导的耐热性的潜在分子机制。结果 ILK 过度表达使肿瘤细胞对热疗的细胞杀伤作用具有明显更强的抵抗力。这在分子水平上与热应激诱导的应激激活蛋白激酶/c-Jun-NH(2)-末端激酶、p38 丝裂原激活蛋白激酶活性和 caspase 9 活性的下调相关。 ILK 的过度表达还被证明可诱导小鼠前列腺癌细胞系中更快的肿瘤生长 结论 ILK 在肿瘤生长和肿瘤对热疗治疗的反应中发挥重要作用。
PURPOSE Integrin-linked kinase (ILK) is a serine-threonine kinase associated with anchorage-independent growth and tumorigenic transformation. Previous studies indicate that overexpression of ILK is common among several types of tumors, and it is involved in the regulation of tumor cell survival under stress. In this study, we examined the effects of ILK expression on tumor cellular response to hyperthermia. EXPERIMENTAL DESIGN We used an adenovirus-mediated approach to overexpress the ILK gene in a prostate cancer cell line and examine its effects on heat stress-induced cell death. Clonogenic survival, as well as apoptosis, was evaluated in cells that overexpress ILK. In addition, the ability to form tumors in vivo was examined in syngeneic hosts. Finally, potential molecular mechanisms of ILK-mediated resistance to heat were examined by determining the status of a variety of signal transduction pathways. RESULTS ILK overexpression made tumor cells significantly more resistant to the cell-killing effects of hyperthermia. This was correlated at the molecular level with the down-regulation of hyperthermia-induced activation of stress-activated protein kinase/c-Jun-NH(2)-terminal kinase, p38 mitogen-activated protein kinase activities, and caspase 9. The overexpression of ILK was also shown to induce a more rapid tumor growth in a murine prostate cancer cell line CONCLUSION ILK plays an important role in tumor growth and tumor response to hyperthermia treatment.