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Alterations in transforming growth factor-alpha and epidermal growth factor receptor expression during rat esophageal
Q S Wang1, C L Sabourin, G N Bijur
1Department of Preventive Medicine, Ohio State University, Columbus, USA.
Abstract:
Transforming growth factor-alpha (TGF-alpha) stimulates cell proliferation through interaction with its receptor, the epidermal growth factor receptor (EGFR), by activating its tyrosine kinase activities. The simultaneous overexpression of TGF-alpha and EGFR by tumor cells is thought to trigger the autocrine growth pathway, leading to uncontrolled proliferation. To examine their roles in rat esophageal tumorigenesis induced by the chemical carcinogen N-nitrosomethylbenzylamine (NMBA), TGF-alpha, and EGFR expression was evaluated in normal rat esophageal epithelium, in NMBA-induced preneoplastic lesions, and in papillomas by quantitative reverse transcription-polymerase chain reaction (RT-PCR), in situ hybridization, and immunohistochemical analyses. Compared with the levels in normal epithelium, the TGF-alpha and EGFR mRNA levels in esophageal papillomas were 3.6 and 1.9 times higher, respectively. In the preneoplastic epithelium, although a trend of increased TGF-alpha and EGFR mRNA levels was observed, collectively there were no significant differences between preneoplastic and normal samples by RT-PCR analysis. In situ hybridization and immunohistochemical staining showed increased levels of TGF-alpha and EGFR mRNA and protein products in papillomas and in pronounced hyperplastic and dysplastic lesions. TGF-alpha and EGFR expression correlated with each other and with the expression of proliferating cell nuclear antigen, a marker for cell proliferation. These results suggest that disregulation of TGF-alpha and EGFR expression may contribute to autonomous cell growth and may play an important role in rat esophageal tumorigenesis induced by NMBA.
Insights
Transforming growth factor-alpha (TGF-alpha) and epidermal growth factor receptor (EGFR) are upregulated in rat esophageal tumors. Their dysregulation contributes to uncontrolled cell growth and esophageal tumorigenesis.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Transforming growth factor-alpha (TGF-alpha) and epidermal growth factor receptor (EGFR) signaling pathways are crucial for cell proliferation.
- Overexpression of TGF-alpha and EGFR can lead to autocrine growth and uncontrolled proliferation, implicated in tumorigenesis.
Purpose of the Study:
- To investigate the roles of TGF-alpha and EGFR in N-nitrosomethylbenzylamine (NMBA)-induced rat esophageal tumorigenesis.
- To evaluate the expression levels of TGF-alpha and EGFR in normal, preneoplastic, and neoplastic esophageal tissues.
Main Methods:
- Quantitative reverse transcription-polymerase chain reaction (RT-PCR) for mRNA analysis.
- In situ hybridization and immunohistochemical analyses for mRNA and protein localization and quantification.
- Correlation analysis with proliferating cell nuclear antigen (PCNA) as a cell proliferation marker.
Main Results:
- TGF-alpha and EGFR mRNA levels were significantly higher (3.6-fold and 1.9-fold, respectively) in esophageal papillomas compared to normal epithelium.
- While preneoplastic lesions showed a trend, RT-PCR did not reveal significant differences in TGF-alpha and EGFR mRNA levels compared to normal tissue.
- Increased TGF-alpha and EGFR mRNA and protein were observed in papillomas and hyperplastic/dysplastic lesions, correlating with each other and with PCNA expression.
Conclusions:
- Disregulation of TGF-alpha and EGFR expression is implicated in the development of rat esophageal tumors induced by NMBA.
- The coordinated upregulation of TGF-alpha and EGFR contributes to autonomous cell growth in esophageal tumorigenesis.
- These findings highlight the potential role of the TGF-alpha/EGFR pathway in driving esophageal cancer progression.