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Overexpression of protein tyrosine kinases in human esophageal cancer
1Division of Clinical Pathology, Faculty of Medicine, Tokyo Medical and Dental University, Japan. nemoto-path@med.tmd.ac.jp
Abstract:
Using a PCR-based cloning technique, we isolated a series of protein tyrosine kinases (PTKs) expressed in a cell line of esophageal squamous cell carcinoma. Sequence analysis revealed 10 different kinds of PTKs of the receptor type [epidermal cell growth factor receptor, insulin-like growth factor I receptor, fibroblast growth factor receptor 4, eck, erk, discoidin domain receptor (DDR)/trkE/cell adhesion kinase (Cak), HEK2, HEK8, axl and sky] and one PTK of the nonreceptor type (tyk2). Subsequently, we examined the expression of the transcripts of these 11 genes in paired samples of normal and carcinomatous esophageal tissues obtained from 12 cases of esophageal cancer. We found that all 11 gene transcripts were expressed in both carcinomatous and normal tissues, and 6 of them were significantly overexpressed in carcinomatous tissues relative to adjacent normal tissues. Among these, the magnitude of mRNA expression of DDR/trkE/Cak PTK was positively correlated with the proliferative activity of carcinoma cells, but not with their degree of differentiation. Immunohistochemically, DDR was expressed in both normal and cancerous esophageal cells. The intensity of the expression was higher in cancer than normal tissue. In addition, we confirmed the expression of two isoforms of DDR/trkE/Cak in normal and cancerous esophagus. Our study suggests that DDR/trkE/Cak plays an important role in the regulation of proliferation of esophageal cancer.
Insights
This study identified 11 protein tyrosine kinases (PTKs) in esophageal cancer cells. Discoidin domain receptor (DDR)/trkE/cell adhesion kinase (Cak) PTK was overexpressed in tumors and linked to cancer cell proliferation.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Esophageal squamous cell carcinoma (ESCC) is a significant global health concern.
- Protein tyrosine kinases (PTKs) are crucial regulators of cell signaling implicated in cancer development.
- Understanding PTK expression in ESCC is vital for identifying potential therapeutic targets.
Purpose of the Study:
- To identify and characterize PTKs expressed in ESCC.
- To investigate the differential expression of PTKs in cancerous versus normal esophageal tissues.
- To explore the correlation between PTK expression and clinicopathological features of ESCC, particularly proliferation.
Main Methods:
- Polymerase chain reaction (PCR)-based cloning was used to isolate PTK genes from an ESCC cell line.
- Quantitative analysis of gene transcript expression in paired normal and tumor tissues from 12 ESCC patients.
- Immunohistochemical staining to assess protein expression and localization of DDR.
- Analysis of DDR isoforms in normal and cancerous esophageal tissues.
Main Results:
- Eleven PTKs were identified, including 10 receptor-type and 1 nonreceptor-type.
- All 11 PTK transcripts were expressed in both normal and cancerous tissues.
- Six PTKs were significantly overexpressed in tumor tissues compared to adjacent normal tissues.
- mRNA expression of Discoidin domain receptor (DDR)/trkE/cell adhesion kinase (Cak) PTK positively correlated with carcinoma cell proliferation.
- DDR protein expression was elevated in cancer tissues, with two isoforms confirmed in both normal and cancerous esophagus.
Conclusions:
- DDR/trkE/Cak PTK is frequently overexpressed in esophageal squamous cell carcinoma.
- DDR/trkE/Cak expression is associated with increased proliferation of esophageal cancer cells.
- DDR/trkE/Cak represents a potential therapeutic target for managing esophageal cancer proliferation.