Progression of esophageal carcinoma by loss of EGF-STAT1 pathway.
OBJECTIVE
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 (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 significance of this EGF-STAT1 pathway.


METHODS
A series of cultured cell lines that had been established from surgical specimens of esophageal squamous cell carcinoma was studied for the existence of the EGF-STAT1 pathway. Normal esophageal squamous epithelial cells either explanted from non-neoplastic 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 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 had a dramatically better prognosis.


CONCLUSIONS
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 esophageal cancer and could lead to the development of useful clinical applications.
Watanabe
G
G
Department of Surgery and Surgical Basic Science, Graduate School of Medicine, Kyoto University, Japan.
Kaganoi
J
J
Imamura
M
M
Shimada
Y
Y
Itami
A
A
Uchida
S
S
Sato
F
F
Kitagawa
M
M
D015152:Blotting, Northern; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018450:Disease Progression; D066246:ErbB Receptors / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology; D004947:Esophagus / Q000166:cytology; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D050794:STAT1 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D015534:Trans-Activators; D066246:ErbB Receptors