Expression of Epidermal Growth Factor, Transforming Growth Factor Alpha and Their Receptor in Gastro-Oesophageal Diseases

Abstract

This article is a review of aspects of the expression of the regulatory peptides; epidermal growth factor (EGF), transforming growth factor alpha (TGF-α), and their receptor (EGF-R) in the epithelium of the human oesophagus and stomach in health and disease. It has become clear that TGF-α has increased expression in metaplastic, dysplastic and neoplastic tissue of the oesophagus compared with normal mucosa. The degree of abnormal expression becomes more marked as dysplasia increases. TGF-α expression is also increased in gastric neoplasias. EGF has a different pattern of expression, being decreased in oesophagitis and increased in gastritis. Although EGF is present in Barrett’s oesophagitis, the expression of EGF does not discriminate between dysplastic and neoplastic epithelium. EGF-R is normally expressed on all gastrointestinal epithelia, but its expression is increased in Barrett’s epithelium, as well as in adenocarcinomas of the oesophagus and the stomach. The two peptides bind to their receptors on the mucosal cell membranes, and the co-expression of peptide and receptor is positively associated with varying degrees of cellular proliferation. The density of receptor expression may modulate the proliferative stimulus, leading to either mitogenic (regulated) or oncogenic (unregulated) growth.

Microtubule inhibition causes epidermal growth factor receptor inactivation in oesophageal cancer cells

“…It has been reported that EGFR is commonly overexpressed in oesophageal carcinoma (14). Variable but detectable levels of EGFR were observed in all 9 oesophageal carcinoma cell lines used in this study (Fig.…”

“…Thus, there is an urgent need to improve current therapies. In oesophageal carcinoma patients, EGFR has been reported to be commonly overexpressed (14) and the overexpression is correlated to lymph node metastasis, vascular invasion and shorter survival (15)(16)(17). The EGF and TGF ligands function as mitogens for oesophageal tumour cells (18) and activation of EGFR signalling has been implicated in metastasis via modulation of cell adhesion, angiogenesis, invasion and migration.…”

Molecular Biology of Barrett’s Adenocarcinoma

“…Although EGF is also expressed in BE, the expression of EGF does not discriminate between dysplastic and neoplastic epithelium. 110 Overexpression of EGFR in the esophagus correlated with the degree of mucosal dysplasia and the occurrence of adenocarcinoma, suggesting that high expression levels may reflect increased malignant transformation potential in BE. 25,110 -112 Al-Kasspooles et al 113 found EGFR gene amplification in 30% of the esophageal adenocarcinomas and also in Barrett's metaplasia, but no correlation with the level of EGFR expression by immunohistochemistry.…”

“…TGF-␣ expression is increased in metaplastic, dysplastic, and neoplastic tissue of the esophagus compared with normal mucosa. 110 The degree of abnormal expression becomes more marked as dysplasia increases and correlates with the proliferative indices in BE. 22,110,114 In summary, EGF/TGF-␣ and their receptor EGFR are important in the progression of normal esophageal squamous epithelium to metaplasia, dysplasia, and finally carcinoma and may be associated with autocrine growth regulation in normal gastrointestinal mucosa and neoplasia.…”

Activation of Growth Factor Receptors in Esophageal Cancer—Implications for Therapy

“…EGFR is often overexpressed in esophageal cancers, both squamous cell carcinoma and adenocarcinoma, which in certain cases also express the ligands EGF or transforming growth factor ␣ (TGF-␣), establishing autocrine growth-promoting loops [11][12][13][14][15][16][17][18][19][20]. In fact, EGFR overexpression has been demonstrated to correlate with poor prognosis [16,[21][22][23][24]].…”