title: Alterations of ubiquitylation and sumoylation in conventional renal cell carcinomas after the Chernobyl accident: a comparison with Spanish cases.
abstract: We determined whether ubiquitylation and sumoylation processes are involved in conventional renal cell carcinogenesis associated with chronic, long-term, persistent low doses of ionizing radiation (IR) in patients living for more than 20 years in cesium-137 ((137)Cs)-contaminated areas after the Chernobyl accident in Ukraine. To this end, we assessed the immunohistochemical expression of ubiquitin (Ub), SUMO1, SUMO E2 conjugating enzyme Ubc9, and the cell cycle regulators p53, mdm2, and p14(ARF) in 38 conventional renal cell carcinomas from Ukrainian patients with different degrees of radiation exposure after the Chernobyl accident. As control cases, 18 conventional renal carcinoma (cRCC) tissues from a Spanish cohort were analyzed. No significant differences between the Ukrainian and Spanish groups were found regarding Ub overexpression, although being higher in the Ukrainian cases. Furthermore, this expression was inversely associated with SUMO1 and Ubc9, with no correlation with tumor nuclear grade. There was also a direct relationship between Ubc9 and inflammatory response. These findings do not allow us to consider the immunohistochemical expression of ubiquitylation and sumoylation as valuable markers for discriminating the effects of long-term, low-dose IR exposure in cRCC carcinogenesis.
authors.affiliation: Department of Pathology, Medical School of Valencia University, Avda. Blasco Ibáñez 17, 46010, Valencia, Spain.
authors.forename: Luisa
authors.initials: L
authors.lastname: Morell-Quadreny
authors.forename: Alina
authors.initials: A
authors.lastname: Romanenko
authors.forename: Jose Antonio
authors.initials: JA
authors.lastname: Lopez-Guerrero
authors.forename: Silvia
authors.initials: S
authors.lastname: Calabuig
authors.forename: Alexander
authors.initials: A
authors.lastname: Vozianov
authors.forename: Antonio
authors.initials: A
authors.lastname: Llombart-Bosch
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology; D047852:Chernobyl Nuclear Accident; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D015994:Incidence; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D007680:Kidney Neoplasms / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009381:Neoplasms, Radiation-Induced / Q000378:metabolism / Q000473:pathology; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism; D025842:SUMO-1 Protein / Q000378:metabolism; D013030:Spain; D058207:Sumoylation; D025803:Tumor Suppressor Protein p14ARF / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism; D054875:Ubiquitination; D014455:Ukraine; D015854:Up-Regulation; D000098843:Ubiquitin-Conjugating Enzyme UBC9
chemical_list: D025842:SUMO-1 Protein; C495501:SUMO1 protein, human; C495901:TP53 protein, human; D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53; D044763:Ubiquitin-Conjugating Enzymes; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D000098843:Ubiquitin-Conjugating Enzyme UBC9