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

EGF-STAT信号通路在正常食管鳞状细胞(NESC)和食管鳞癌(SCC)中均有表达，在本实验室已建立的三种食管鳞癌细胞系中，EGF-STAT信号通路均有表达。在这些细胞系中，EGF刺激对活细胞的生长抑制作用显着增加。我们通过Caspase和Bc1-2/Bax家族的级联反应证实了细胞凋亡的证据。另一方面，在NESC中，用原代培养的方法证实了EGF刺激STAT1和STAT3的激活，但没有明显的细胞死亡的证据。我们认识到，即使在信号转导相同的情况下，正常细胞和癌细胞的表型也存在显著差异。此外，免疫细胞化学显示EGF刺激的NESC中STAT1和STAT3在细胞核内聚集，并在体内显示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，未来还需要对正常细胞的生物学意义进行进一步的评估。在我们的实验结果假设的治疗模型中，证实了干扰素γ通过凋亡抑制细胞生长的作用。EGF-STAT信号通路在许多SCC细胞系中均有缺失，提示EGF-STAT信号通路可能具有肿瘤抑制作用。还需要进一步研究其他致病因素以及这些因素的生物学意义。通过这项研究，我们的研究可能会对食道癌的治疗有所帮助。

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.