Progression of esophageal carcinoma by loss of EGF-STAT1 pathway

PURPOSE In only a very limited number of cultured cell lines, epidermal gro wth factor (EGF), a potent mitogen for many kinds of cells, was shown to ac tivate STAT1 (signal transducer and activator of transcription 1) protein, which can transmit signals that cause cell growth arrest and apoptosis. The purpose of this work is to elucidate the physiologic and/or pathological s ignificance of this EGF-STAT1 pathway. MATERIALS AND METHODS A series of cultured cell lines that had been establi shed from surgical specimens of esophageal squamous cell carcinoma was stud ied for the existence of the EGF-STAT1 pathway. Normal esophageal squamous epithelial cells either explanted from nonneoplastic portions of surgically removed human esophageal tissue or in bovine esophageal epithelium in situ were examined as well. RESULTS EGF treatment leads to a strong growth arrest in three of the 30 es ophageal squamous cell carcinoma cell lines. STAT1. was found to be activat ed by EGF in the three cell lines but not in the others. EGF can also activ ate STAT1 in cultured normal esophageal squamous epithelial cells. STAT1 is at the activated state in the basal cell layer of the bovine esophageal ep ithelium. Notably, patients who had harbored the cancer cells with the EGF- STAT1 pathway had a dramatically better prognosis. DISCUSSION 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 a significantly more malignant clinical course. These findings may point out a critical step in the progression of esophage al cancer and could lead to the development of useful clinical applications .