Study of the effects of epidermal growth factor on genomic instability and malignant phenotype of oral squamous cell carcinoma cells

表皮生长因子对口腔鳞癌细胞基因组不稳定性及恶性表型影响的研究

• 批准号: 14571907
• 负责人: NAGAYASU Hiroki
• 金额: $ 1.86万
• 依托单位: Health Sciences University of Hokkaido
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571907/
• 关键词: EGF; invasion; metastasis; malignant pehenotype; cell motility; genomic instability; 浸潤能; 運動能; 悪性化進展; 遺伝子不安定性; 活性酸素

Growth factors can enhance the malignant potential of tumor cells. To study the effects of epidermal growth factor(EGF) on invasion and metastasis of human oral squamous cell carcinoma, we examined the intercellular signal transduction of EGP-induced motility using an EGF sensitive S-1 clone cell line, obtained from Ca9-22 cell line. EGF -treatde S-1 cells were affected some blocking chemicals, and moduration of random motility was examined by phagokinetic track assay.When the cells were treated with erbstatin analog; to inhibit tyrosine phosphorylation, or psi-tectorigenin to inhibit phosphatidyl-inositol turnover the motility enhanced by EGF was completely inhibited. When phorbol 12-myristate 13-acetate(PMA) was used, to stimulate protein kinase C(PKC), motility in the absence of EGF was enhanced similar to that of EGF stimulation. Calphostin C, an inhibitor of PKC activation, completely eliminated the EGF-induced enhancement of motility. Examination of the intercellularlocalization of PKC with a confocal laser microscope showed enhanced expression of PKC and transduction of PKC to membrane area after EGF stimulation. These results suggest that activation of phospholipase C-v (PLC) caused by auto-phosphorylation of EGF receptor might play an important role in the signal transduction of EGF induced cell motility.To examine the relationship between growth factor and tumor progression, we pleviously established a weakly malignant cell line, ER-1, from rat mammary carcinoma cell line in female SHR rat. We found that a 24-hour exposure of ER-1 celisto EGF induced malignant properties that were reversible but that, after a 1-month exposure, these changes were irreversible. In DNA fingerprinting as abnormal bands were observed in ER-I cells after long-term EGE stimulation. These results suggest that long-term EF stimulation can affect the genomic instability of ER-I cells.

生长因子可以增强肿瘤细胞的恶性潜能。为了研究表皮生长因子（EGF）对人口腔鳞状细胞癌侵袭和转移的影响，我们使用从 Ca9-22 细胞获得的 EGF 敏感 S-1 克隆细胞系检测了 EGP 诱导的运动的细胞间信号转导。线。 EGF处理的S-1细胞受到一些阻断化学物质的影响，并通过吞噬动力学轨迹测定检查随机运动的调节。抑制酪氨酸磷酸化，或 psi-鸢尾素抑制磷脂酰肌醇转换，EGF 增强的运动被完全抑制。当使用佛波醇12-肉豆蔻酸酯13-乙酸酯(PMA)刺激蛋白激酶C(PKC)时，在没有EGF的情况下运动性增强，类似于EGF刺激。 Calphostin C 是一种 PKC 激活抑制剂，可完全消除 EGF 诱导的运动增强。用共焦激光显微镜检查 PKC 的细胞间定位显示，EGF 刺激后 PKC 表达增强，并且 PKC 转导至膜区域。这些结果表明，EGF受体自身磷酸化引起的磷脂酶C-v（PLC）的激活可能在EGF诱导的细胞运动的信号转导中发挥重要作用。为了检查生长因子与肿瘤进展之间的关系，我们之前建立了弱的模型恶性细胞系，ER-1，来自雌性 SHR 大鼠的大鼠乳腺癌细胞系。我们发现，暴露 24 小时 ER-1 Celisto EGF 会诱发可逆的恶性特性，但暴露 1 个月后，这些变化是不可逆的。在DNA指纹分析中，长期EGE刺激后在ER-I细胞中观察到异常条带。这些结果表明长期 EF 刺激可以影响 ER-1 细胞的基因组不稳定性。

项目成果

Hiroyuki Kitajyo, Toshiyuki Shibata, Hiroki Nagayasu, Takashi Kawano, Jun-ichi Hamada, Tomomi Yamashita, Makoto Arisue: "Rho regulates the hepatocyte growth factor/scatter factor-stimulated cell motility of human oral squamous cell carcinoma cells"Oncolog

Hiroyuki Kitajyo、Toshiyuki Shibata、Hiroki Nagayasu、Takashi Kawano、Jun-ichi Hamada、Tomomi Yamashita、Makoto Arisue：“Rho 调节人口腔鳞状细胞癌细胞的肝细胞生长因子/散射因子刺激的细胞运动”Oncolog

Hiroyuki Kitajyo, Toshiyuki Shibata, Hiroki Nagayasu, et al.: "Rho regulates the hepatocyte growth factor/scatter factor-stimulated cell motility of human oral squamous cell carcinoma cells"Oncology reports. 10. 1351-1356 (2003)

Hiroyuki Kitajyo、Toshiyuki Shibata、Hiroki Nagayasu 等人：“Rho 调节人口腔鳞状细胞癌细胞的肝细胞生长因子/散射因子刺激的细胞运动”肿瘤学报告。