P16INK4A and p15INK4B gene alteration associated with oxidative stress in renal cell carcinomas after the chernobyl accident (pilot study)
| Autor: | Antonio Pellín, Antonio Llombart-Bosch, Valentin Nepomnyaschy, José Antonio López-Guerrero, Alina Romanenko, Luisa Morell-Quadreny, Alexander Vozianov |
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| Rok vydání: | 2002 |
| Předmět: |
Adult
Male Pathology medicine.medical_specialty Adolescent Cell Cell Cycle Proteins Pilot Projects medicine.disease_cause Polymerase Chain Reaction Pathology and Forensic Medicine Immunoenzyme Techniques Carcinoma medicine Biomarkers Tumor Humans Molecular Biology Carcinoma Renal Cell Cyclin-Dependent Kinase Inhibitor p16 Aged Cyclin-Dependent Kinase Inhibitor p15 Neoplasm Staging biology business.industry Tumor Suppressor Proteins Promoter Cell Biology DNA Neoplasm DNA Methylation Middle Aged medicine.disease Kidney Neoplasms Nitric oxide synthase Oxidative Stress medicine.anatomical_structure DNA methylation biology.protein Immunohistochemistry Histopathology Female business Radioactive Hazard Release Ukraine Oxidative stress Power Plants |
| Zdroj: | Diagnostic molecular pathology : the American journal of surgical pathology, part B. 11(3) |
| ISSN: | 1052-9551 |
| Popis: | Our study was undertaken to better understand the role of G1/S transition abnormalities in the malignant progression of renal cell carcinomas (RCCs), exposed to long-term low doses of ionizing radiation (IR), from patients living in radiocontaminated areas of the Ukraine after the Chernobyl accident. We studied p16 and p15 gene alteration in association with oxidative stress markers, including inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2). We analyzed 88 samples collected from 22 patients with RCCs and with different exposure to IR. Homozygous deletion of the p16 and p15 genes, as well as hypermethylation of the 5CpG island in the promoter region of the same genes, were analyzed by differential PCR and Methylation-Specific PCR respectively, in association with histopathology and immunohistochemical analysis of p16 and p15 proteins. COX2 and iNOS expression in the same tumors were likewise analyzed. Aberrant hypermethylation was observed in 7 (32%) and 5 (23%) cases accompanied, by immunohistochemical loss of expression for p16 and p15 genes respectively, in both high stage and grade tumors from patients living in radiocontaminated areas, this being especially outstanding for the p16 gene. An association with COX2 and less iNOS overexpression in the same tumors was observed. Our data suggest that inactivation of p16 gene, but not p15, induced by increased oxidative stress generated by persistent chronic exposure to IR, could be one of the major pathways responsible for RCCs malignant progression. |
| Databáze: | OpenAIRE |
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