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Progression of esophageal carcinoma by loss of EGF-STAT1 pathway
G Watanabe1, J Kaganoi, M Imamura
1Department of Surgery and Surgical Basic Science, Graduate School of Medicine, Kyoto University, Japan.
Purpose:
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.
Materials And 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.
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 esophageal cancer and could lead to the development of useful clinical applications.
Insights
The epidermal growth factor (EGF)-STAT1 pathway induces growth arrest in esophageal cancer cells. Loss of this pathway is linked to a worse prognosis, suggesting its importance in esophageal cancer progression.
Area of Science:
- Oncology
- Molecular Biology
- Cell Signaling
Background:
- Epidermal growth factor (EGF) is a mitogen that can activate STAT1 (signal transducer and activator of transcription 1) in some cell lines, leading to growth arrest and apoptosis.
- The role of the EGF-STAT1 pathway in esophageal squamous cell carcinoma (ESCC) and normal esophageal epithelium is not well understood.
Purpose of the Study:
- To investigate the presence and significance of the EGF-STAT1 pathway in ESCC cell lines and normal esophageal tissues.
- To determine the correlation between the EGF-STAT1 pathway and patient prognosis in ESCC.
Main Methods:
- Examined a series of cultured ESCC cell lines and normal esophageal epithelial cells (human and bovine) for the EGF-STAT1 pathway.
- Assessed STAT1 activation in response to EGF treatment.
Main Results:
- EGF treatment induced growth arrest and STAT1 activation in 3 out of 30 ESCC cell lines.
- The EGF-STAT1 pathway was also observed in cultured normal esophageal epithelial cells and in vivo in bovine esophageal epithelium.
- Patients with ESCC exhibiting the EGF-STAT1 pathway had a significantly better prognosis.
Conclusions:
- The EGF-STAT1 pathway appears to be a feature of normal esophageal epithelial cells and is frequently lost in ESCC.
- Loss of the EGF-STAT1 pathway is associated with a more aggressive clinical course in esophageal cancer.
- This pathway represents a potential target for clinical applications in esophageal cancer treatment.
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