Increased Expression and Secretion of Interleukin-6 in Patients with Barrett’s Esophagus
Autor: | Hana Holubec, Anil Prasad, Harris Bernstein, Richard E. Sampliner, Katerina Dvorakova, Bohuslav Dvorak, Harinder S. Garewal, Ronnie Fass, Jessica A. Dominguez, Claire M. Payne, Haiyan Cui, Lois Ramsey, Carol Bernstein |
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Rok vydání: | 2004 |
Předmět: |
Adult
Cancer Research Pathology medicine.medical_specialty Esophageal Neoplasms Duodenum Biology Polymerase Chain Reaction Malignant transformation Barrett Esophagus Risk Factors medicine Humans Intestinal Mucosa Esophagus Interleukin 6 Aged Interleukin-6 Interleukin Middle Aged medicine.disease Immunohistochemistry Epithelium Cell Transformation Neoplastic medicine.anatomical_structure Gene Expression Regulation Oncology Barrett's esophagus Cancer research biology.protein STAT protein |
Zdroj: | Clinical Cancer Research. 10:2020-2028 |
ISSN: | 1557-3265 1078-0432 |
DOI: | 10.1158/1078-0432.ccr-0437-03 |
Popis: | Purpose: Barrett’s esophagus (BE) is a common premalignant lesion of the distal part of the esophagus that arises as a consequence of chronic duodenogastroesophageal reflux. Interleukin (IL)-6 is a pleiotropic cytokine that regulates immune defense mechanisms and hematopoiesis. In addition, IL-6 may also be involved in malignant transformation and tumor progression. IL-6 has been shown to inhibit apoptosis. The major aim of this study was to evaluate expression of IL-6 in BE at the protein and mRNA levels. In addition, we tested whether proteins that are associated with IL-6 signaling, phosphorylated signal transducer and activator of transcription 3 and two antiapoptotic proteins, Bcl-xL and Mcl-1, are also expressed in the same tissues.Experimental Design: Biopsies of duodenum, BE, and squamous epithelium were evaluated by using a human cytokine protein array, ELISA, real-time PCR, and immunohistochemistry.Results: Increased IL-6 levels were found to be secreted from BE tissue compared with duodenum or squamous epithelium from sites adjacent or 5 cm away from the BE lesion. IL-6 mRNA was also elevated in BE compared with duodenum or squamous epithelium in five of seven patients. Immunohistochemical studies confirmed IL-6 expression in intestinal glandular epithelium in BE tissue. Activated signal transducer and activator of transcription 3, Mcl-1, and Bcl-xL are present at higher levels in BE glands, with lower levels being found in duodenum or squamous epitheliumConclusions: These data, taken together, suggest that elevated IL-6 levels in BE may contribute to the development of apoptosis resistance, thereby placing this epithelium at higher risk of developing malignancy. |
Databáze: | OpenAIRE |
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