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）和食管鳞状细胞癌（SCC）中均存在，在本实验室建立的3株食管鳞癌细胞系中均存在EGF-STAT信号通路。在这些细胞系中，证明了EGF刺激对活细胞的生长抑制显著增加。在NESC中，通过原代培养的方法证实了EGF刺激后STAT 1和STAT 3的激活，但没有发现明显的细胞死亡的证据。我们认识到，即使在信号传导相同的情况下，正常细胞和癌细胞之间也存在显著的表型差异。此外，使用免疫细胞化学证实了在NESC中通过EGF刺激的STAT 1和STAT 3的细胞核积聚，并且在体内显示了它们的蛋白质活化。我们认为EGF-STAT信号通路在NESC和SCC中发挥了重要作用，其在正常细胞中的生物学意义有待进一步研究。在我们的实验结果所设想的治疗模型中，IFN γ通过凋亡抑制细胞生长的作用得到了证实。EGF-STAT信号通路在许多SCC细胞系中存在缺失，提示EGF-STAT信号通路在SCC细胞中起抑癌作用，本文对EGF-STAT信号通路作为生长抑制因子的作用进行综述。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。本研究对食管癌的治疗有一定的参考价值。

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.