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

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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.