Physiological significance of EGF/STAT1 pathway

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In only a very limited number of cultured cell lines, epidermal growth factor (EGF), a potent mitogen for many kinds of cells, was shown to activate STAT1 (for signal transducer and activator of transcription 1) protein, which can transmit signals causing cell growth arrest and apoptosis. To elusidate physiological and/or pathological significance of this EGF-STAT1 pathway, a series of cultured cell lines which had been established from surgical specimens of esophageal squamous cell carcinoma was studied for the existence of the EGF-STAT1 pathway. EGF treatment leads to a strong growth arrest in three among the 30 esophageal squamous cell carcinoma cell lines. STAT1 was found to be activated by EGF in the three cell lines but not in the others. EGF can also activate STAT1 in cultured normal esophageal squamous epithelial cells. STAT1 is at the activated state in the basal cell layer of the bovine esophageal epithelium. Notably patients who had harbored the cancer cells with the EGF-STAT1 pathway underwent dramatically better prognosis. Thus, the EGF-STAT1 pathway may be intrinsic to esophageal epithelial lineage of cells, and is lost in a considerable fraction of the carcinomas. This loss appears to cause significantly more malignant clinical course to the patients. These findings may point out a critical step in the progression of the esophageal cancer and could lead to the development of useful clinical applications.