The INK4a /ARF locus: role in cell cycle control for renal cell epithelial tumor growth after the Chernobyl accident

Virchows Archiv : an International Journal of Pathology
Alina RomanenkoAntonio Llombart-Bosch

Abstract

Previous studies have shown that during the period subsequent to the Chernobyl accident, increases in morbidity, aggressivity and proliferative activity of renal-cell carcinomas (RCCs) in Ukrainian patients were recognized. The present paper describes the molecular alterations of those tumor suppressor genes located on chromosome 9p21 ( INK4a/ARF locus and p15(INK4B)) in 26 primary renal-cell epithelial tumors from patients with different degrees of radiation exposure after the Chernobyl accident in Ukraine. Radiometric measurement of Cesium 137 ((137)Cs) was conducted with 1-day urine from all patients before surgery. Our results demonstrate that RCCs from patients living in the radio-contaminated areas showed aberrant hypermethylation of p14(ARF) and p16(INK4A) genes, associated with increased p38MAPK, p14(ARF), mdm2, cyclinD1 and Ki67 protein expression levels. Present findings show the possibility that chronic long-term low-dose radiation activates the INK4a/ARF locus, targeted by activation of the p38MAPK cascade. These actions could lead to disruptions and loss of cell cycle checkpoints and, thereby, to cellular transformation.

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Citations

Oct 7, 2008·The Cancer Journal·Wong-Ho Chow, Susan S Devesa
Jul 27, 2011·Renal Failure·Viroj Wiwanitkit
Aug 23, 2020·International Journal of Molecular Sciences·Mauro Belli, Maria Antonella Tabocchini

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