Loss of function of Trp53, but not Apc, leads to the development of esophageal adenocarcinoma in mice with jejunoesophageal reflux
| Autor: | Peter W. Laird, Megan E. McGarvey, Jeffrey H. Peters, Darryl Shibata, Martin Fein, Kristin A. Skinner, Para Chandrasoma, Nicole Baril |
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| Rok vydání: | 1999 |
| Předmět: |
Adenoma
medicine.medical_specialty Pathology Genes APC Tumor suppressor gene Esophageal Neoplasms animal diseases Biology Adenocarcinoma Gastroenterology Epithelium Barrett Esophagus Mice Esophagus Metaplasia Internal medicine medicine Carcinoma Animals Mice Knockout Jejunal Neoplasms Esophageal disease Reflux Histology Jejunal Diseases medicine.disease Genes p53 digestive system diseases medicine.anatomical_structure Mutation Gastroesophageal Reflux Surgery medicine.symptom |
| Zdroj: | The Journal of surgical research. 83(1) |
| ISSN: | 0022-4804 |
| Popis: | Introduction. APC and TP53 are tumor suppressor genes known to be altered frequently in human esophageal adenocarcinoma (EAC), which arises as a complication of reflux disease. To determine the functional role of these genes in the development of EAC, we have created reflux in mice gene-targeted for either Trp53 or Apc. Methods. Wild-type (WT), p53-knockout ( Trp53 −/− ), or Apc -mutated ( Apc Min/+ ) mice were generated in our breeding colony. Total gastrectomy with esophagojejunostomy was performed at 6 weeks of age, creating jejunoesophageal reflux. Unoperated control mice were maintained under identical conditions. Mice were sacrificed at 30 weeks of age. Histology of the esophagus and jejunal anastamosis or gastroesophageal junction was reviewed by a single pathologist blinded to the genotype of the animal. Results. The esophagus was normal in all of the unoperated mice (6 Apc Min/+ , 6 WT, and 6 Trp53 −/− ). All operated mice (6 Apc Min/+ , 12 WT, and 4 Trp53 −/− ) had esophagitis, with squamous hyperplasia and early focal ulceration. Barrett's metaplasia was identified in 33% of the operated Apc Min/+ (2/6) and 25% of the Trp53 −/− (1/4) mice, but not in the WT mice. Of 4 operated Trp53 −/− mice, all developed severe dysplasia of the squamous epithelium and 2 (50%) had EAC on histology, although no gross tumors were seen. No severe dysplasia or carcinoma was identified in any of the Apc Min/+ or WT mice. Conclusions. Loss of either Trp53 or Apc leads to the development of columnar metaplasia, whereas loss of Trp53, but not Apc, leads to development of cancer in mice with jejunoesophageal reflux. |
| Databáze: | OpenAIRE |
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