Department of Pathology, Medical School of Valencia University, Avda. Blasco Ibáñez 17, 46010, Valencia, Spain.
Virchows Arch. 2011 Sep;459(3):307-13. doi: 10.1007/s00428-011-1124-8. Epub 2011 Jul 23.
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.
我们研究了泛素化和 sumoylation 过程是否参与了与乌克兰切尔诺贝利事故后在铯-137((137)Cs)污染区生活超过 20 年的患者慢性、长期、持续低剂量电离辐射(IR)相关的传统肾细胞癌发生。为此,我们评估了 38 例来自乌克兰患者的传统肾细胞癌组织中泛素 (Ub)、SUMO1、SUMO E2 连接酶 Ubc9 以及细胞周期调节剂 p53、mdm2 和 p14(ARF)的免疫组织化学表达水平,这些患者在切尔诺贝利事故后受到不同程度的辐射暴露。作为对照病例,我们分析了来自西班牙队列的 18 例常规肾细胞癌(cRCC)组织。乌克兰组和西班牙组之间在 Ub 过表达方面没有发现显著差异,尽管乌克兰组的 Ub 过表达更高。此外,这种表达与 SUMO1 和 Ubc9 呈负相关,与肿瘤核级无相关性。Ubc9 与炎症反应之间也存在直接关系。这些发现使我们不能将泛素化和 sumoylation 的免疫组织化学表达视为区分 cRCC 癌变中长期低剂量 IR 暴露影响的有价值标志物。