Growth arrest signal in esophageal cancer. Biological significance and clinical implication of EGF-STAT signal transduction system.

食管癌的生长停滞信号。

基本信息

批准号：
10470241
负责人：
SHIMADA Yutaka
金额：
$ 7.3万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10470241/
关键词：
EGF STAT Esophageal cancer Growth arrest signal アポトーシス

项目摘要

EGF-STAT signaling pathway was maintained in both the normal esophageal squamous cell (NESC) and the esophageal squamous cell carcinoma (SCC).In three esophageal SCC cell lines which had been established in our laboratory, EGF-STAT signaling pathway was maintained. In these cell lines a remarkable increase in growth inhibition of viable cells with EGF-stimulation was demonstrated. We were able to show that the evidence of Apoptosis through the cascade of Caspase and Bc1-2/Bax family.In NESC, on the other hand, activation of STAT1 and STAT3 by EGF-stimulation was confirmed using the primary culture method, but obvious evidence of cell death was not demonstrated. We recognized difference in remarkable phenotype between normal cell and cancer cell even when signaling transduction was the same. Furthermore nucleus accumulation of STAT1 and STAT3 by EGF-stimulation in NESC was demonstrated using immunocytochemistry and their activation of protein were showed in vivo. We are suggesting that EGF-STAT signaling pathway played a role in NESC and SCC.A further examination of biological significance in normal cell is needed to be evaluated in the future.In the treatment model supposed from our experiment results, the effect of cell growth inhibition through Apoptosis by interferon gamma was demonstrated. It is suggested that EGF-STAT signaling pathway plays the role of tumor suppressor because the loss of this signaling pathway is recognized in many SCC cell lines.We summarized that EGF-STAT signaling pathway acts as a growth inhibitor. Further investigation of other contributing factors and the biological significance of these factors is needed. With this research our investigation may be useful for the treatment of esophageal cancer.

正常食管鳞状细胞(NESC)和食管鳞状细胞癌(SCC)中均维持了EGF-STAT信号通路。在本实验室建立的3个食管SCC细胞系中均维持了EGF-STAT信号通路。在这些细胞系中，EGF 刺激对活细胞的生长抑制显着增加。我们能够通过 Caspase 和 Bc1-2/Bax 家族的级联显示细胞凋亡的证据。另一方面，在 NESC 中，使用原代培养方法证实了 EGF 刺激对 STAT1 和 STAT3 的激活，但明显没有证明细胞死亡的证据。我们认识到即使信号转导相同，正常细胞和癌细胞之间也存在显着的表型差异。此外，使用免疫细胞化学证明了 NESC 中 EGF 刺激引起的 STAT1 和 STAT3 的核积聚，并且在体内显示了它们对蛋白质的激活。我们认为EGF-STAT信号通路在NESC和SCC中发挥了作用。未来需要进一步检查正常细胞中的生物学意义。在我们的实验结果假设的治疗模型中，细胞生长的影响已证明干扰素γ可通过细胞凋亡来抑制。由于在许多SCC细胞系中都发现了该信号通路的缺失，因此表明EGF-STAT信号通路发挥了抑癌作用。我们总结了EGF-STAT信号通路作为生长抑制剂。需要进一步研究其他影响因素以及这些因素的生物学意义。通过这项研究，我们的研究可能有助于食管癌的治疗。