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

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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 p15INK4B) 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 (137Cs) 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 p14ARF and p16INK4A genes, associated with increased p38MAPK, p14ARF, 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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Acknowledgements

The authors are grateful to Estela Pons and Alejo Sempere for their technical assistance. Source of support: GV01–532 from the Generalitat Valenciana and FIS 01/0702 from the Ministry of Health, Madrid, Spain.

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Authors and Affiliations

  1. Departments of Pathology and Urology, Institute of Urology, Academy of Medical Sciences of Ukraine, 9ª Yu. Kotzubinsky, 04053, Kiev, Ukraine

    Alina Romanenko, Valentin Nepomnyaschy & Alexander Vozianov

  2. Department of Pathology, Medical School of Valencia, Avda Blasco Ibañez 17, 46010 , Valencia, Spain

    Luisa Morell-Quadreny, Antonio Pellin & Antonio Llombart-Bosch

  3. Department of Pathology, Fundacion Instituto Valenciano de Oncologia, C/ Beltran Baguena 8-11, 46009, Valencia, Spain

    Jose Antonio Lopez-Guerrero

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  1. Alina Romanenko
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  2. Luisa Morell-Quadreny
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  3. Jose Antonio Lopez-Guerrero
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  4. Antonio Pellin
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  5. Valentin Nepomnyaschy
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  6. Alexander Vozianov
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  7. Antonio Llombart-Bosch
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Correspondence to Antonio Llombart-Bosch.

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Romanenko, A., Morell-Quadreny, L., Lopez-Guerrero, J.A. et al. The INK4a/ARF locus: role in cell cycle control for renal cell epithelial tumor growth after the Chernobyl accident. Virchows Arch 445, 298–304 (2004). https://doi.org/10.1007/s00428-004-1056-7

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  • DOI: https://doi.org/10.1007/s00428-004-1056-7

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