Induction of glutathione s-transferase-pi in Barrett's metaplasia and Barrett's adenocarcinoma cell lines.

Abstract

Barrett's metaplasia consists of columnar epithelium that replaces the normal esophageal mucosa in patients with chronic gastroesophageal reflux. Because intestinal-type Barrett's metaplasia is the major risk factor for adenocarcinoma development, understanding the mechanisms that predispose the esophageal mucosa to malignant degeneration is clinically important. Glutathione s-transferase (GST)-pi belongs to a class of protective enzymes whose activity has been shown to be much lower in Barrett's metaplasia than in the normal esophagus, where this form of GST is predominant. In the studies described here, using immunocytochemical analysis, we observed higher levels of cytoplasmic GST-pi protein in normal esophageal mucosa than in Barrett's metaplasia. Using northern blot analysis, we also observed lower GST-pi mRNA levels in Barrett's metaplasia than in normal esophagus or adenocarcinomas from the same patients. Using as model systems three Barrett's adenocarcinoma cell lines and short-term organ culture of freshly resected normal esophagus and Barrett's metaplasia, dose-dependent induction of GST-pi mRNA was observed by using butylated hydroxyanisole and dexamethasone. GST-pi mRNA in Barrett's metaplasia was induced up to 2.5-fold with 60 microM butylated hydroxyanisole and nearly fivefold with 320 nM dexamethasone after 24 h. These studies demonstrate the ability to induce protective GST-pi in Barrett's metaplasia and may suggest a mechanism for future chemoprevention studies in patients with this type of epithelium, which is at high risk for malignant degeneration.

• Authors: K R Compton, M B Orringer, D G Beer
• Journal: Molecular carcinogenesis (Mol Carcinog) Vol. 24 Issue 2 Pg. 128-36 (Feb 1999) ISSN: 0899-1987 [Print] United States
• PMID: 10078940 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Isoenzymes
• RNA, Messenger
• GSTP1 protein, human
• Glutathione S-Transferase pi
• Glutathione Transferase

Topics

• Adenocarcinoma (enzymology)
• Barrett Esophagus (enzymology)
• Enzyme Induction
• Esophageal Neoplasms (enzymology)
• Glutathione S-Transferase pi
• Glutathione Transferase (biosynthesis)
• Humans
• Isoenzymes (biosynthesis)
• Organ Culture Techniques
• RNA, Messenger (biosynthesis)
• Tumor Cells, Cultured