Proton pump inhibitors reduce cell cycle abnormalities in Barrett's esophagus
| Autor: | Itzhak Shapira, Zamir Halpern, Eichii Tahara, Jacob Rattan, Waturu Yasui, Mark Umansky, A. Hallak, Shlomo Brill, Hanina Hibshoosh, Nadir Arber, Stephen J. Meltzer |
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| Rok vydání: | 2001 |
| Předmět: |
Adult
Cyclin-Dependent Kinase Inhibitor p21 Male Cancer Research Cyclin E Gene Dosage Biology Barrett Esophagus Cyclin D1 Cyclins Proliferating Cell Nuclear Antigen Metaplasia Genetics medicine Humans Genes Tumor Suppressor Enzyme Inhibitors Molecular Biology Cyclin-Dependent Kinase Inhibitor p16 Aged Southern blot Cyclin Aged 80 and over Esophageal disease Cell Cycle Proton Pump Inhibitors DNA Neoplasm Middle Aged Proton Pumps Cell cycle Anti-Ulcer Agents medicine.disease Immunohistochemistry Molecular biology Gene Expression Regulation Neoplastic Barrett's esophagus Female medicine.symptom |
| Zdroj: | Oncogene. 20:7987-7991 |
| ISSN: | 1476-5594 0950-9232 |
| DOI: | 10.1038/sj.onc.1204947 |
| Popis: | Neoplastic progression in Barrett’s esophagus is a multistep process in which the metaplastic columnar epithelium sequentially evolves through a metaplasia-dysplasiacarcinoma sequence. The expression and DNA copy number of key cell cycle regulatory genes in paired normal and Barrett’s esophagus samples was evaluated. Protein levels were evaluated in 60 formalin-fixed, paraAn-embedded human tissues by immunohistochemistry. DNA copy number from 20 fresh tissue pairs was analysed by Southern blot analysis. All normal mucosal samples expressed the p27 kip1 protein, but did not display appreciable nuclear staining for p16 kip4 , p21 cip1 or cyclins D1 and E. Barrett’s metaplastic specimens displayed increased expression levels of p16 kip4 (74%), p21 cip1 (89%) and cyclins D1 (43%) and E (37%). p27 protein was absent in three cases. There was a significant correlation between the expression of p16 kip4 and cyclin E, and p21 cip1 and p27 kip4 with cyclin D1. DNA analysis did not reveal any amplification or deletion of these genes. Acid suppression, however, was associated with significantly lower expression levels of key cell cycle proteins. Increased expression of key cell cycle regulatory genes appears to occur early in the neoplastic progression associated with Barrett’s esophagus. Treatment with proton pump inhibitors appears to alter this increased expression. Oncogene (2001) 20, 7987‐7991. |
| Databáze: | OpenAIRE |
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