Molecular alterations during development of esophageal adenocarcinoma

Abstract

The incidence of esophageal adenocarcinoma has risen significantly over the last decades. During esophageal carcinogenesis many molecular alterations occur that disrupt essential cellular processes, directing the cell to a rapidly proliferating, immortal state. The chronic inflammation that is present in Barrett's esophagus creates an environment in which such molecular alterations are both induced and tolerated. Here, the novel insights in the molecular mechanisms that underlie the development of esophageal adenocarcinoma are reviewed, focusing on the role of inflammation, angiogenesis, apoptosis inhibition, loss of cell cycle control, and loss of cell-cell adhesion. These novel developments will open new perspectives for diagnosis, treatment, and prevention of esophageal adenocarcinoma.

A novel role for the retinoic acid-catabolizing enzyme CYP26A1 in Barrett's associated adenocarcinoma

“…The pattern of gene expression identified included apoptosis-regulating genes, repression of tumour suppressor genes, de-regulation of cell cycle and activation of growth factor (EGFR) and c-Myc genes. These alterations are similar to the molecular events reported in Barrett's carcinogenesis (reviewed in Bax et al, 2005). Increased retinoid activity has been linked to an abrogation of EGFR signalling (Sah et al, 2002).…”

High-grade dysplasia in Barrett's esophagus is associated with increased expression of calgranulin A and B

“…Adenocarcinoma in BE is thought to develop in a stepwise manner through low-grade dysplasia (LGD) and high-grade dysplasia (HGD) [3]. To date, the cellular and molecular mechanisms leading to neoplastic progression in BE are only partly understood [4,5].…”

Systematic review: the application of molecular pathogenesis to prevention and treatment of oesophageal adenocarcinoma

“…The presence of growth factors in the damaged epithelium is likely to be a component of healing; however, their dysregulation also contributes to carcinogenesis. The ErbB family of tyrosine kinase receptors and their ligands have been implicated in the development of oesophageal adenocarcinoma 63 . This group of receptors and ligands are responsible for stimulating cell proliferation in the gastrointestinal (GI) tract.…”

“…The ErbB family of tyrosine kinase receptors and their ligands have been implicated in the development of oesophageal adenocarcinoma. 63 This group of receptors and ligands are responsible for stimulating cell proliferation in the gastrointestinal (GI) tract. One such ligand is epidermal growth factor (EGF) which has been shown to be aberrantly expressed in inflammation, Barrett's oesophagus and adenocarcinoma.…”