Involvement of Ubiquitination and Sumoylation in Bladder Lesions Induced by Persistent Long-Term Low Dose Ionizing Radiation in Humans

Romanenko, Alina; Kinoshita, Anna; Wanibuchi, Hideki; Wei, Min; Zaparin, Wadim; Vinnichenko, Wladimir; Vozianov, Alexander; Fukushima, Shoji

doi:10.1016/s0022-5347(05)00172-2

Cited by 25 publications

(33 citation statements)

References 15 publications

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“…Moreover, only p53 showed direct relation with high-grade tumors. In contrast with previous results in bladder lesions of patients from Ukrainian contaminated areas [23], our data cannot support that long-term, low-dose IR stimulates signal transduction p14 ARF /p53 pathway in clear cell renal carcinogenesis nor Ub overexpression. However, p14 ARF overexpression with higher score was related to cases of Ukrainian cRCCs.…”

Section: Discussioncontrasting

confidence: 99%

Alterations of ubiquitylation and sumoylation in conventional renal cell carcinomas after the Chernobyl accident: a comparison with Spanish cases

et al. 2011

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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.

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Section: Discussioncontrasting

confidence: 99%

Alterations of ubiquitylation and sumoylation in conventional renal cell carcinomas after the Chernobyl accident: a comparison with Spanish cases

et al. 2011

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“…Genotoxic stress induces sumoylation of a broad number of proteins involved in nuclear functions (Manza et al 2004) as well as proteins involved in important signaling pathways, such as the nuclear factor kappa B (NF-jB) (Huang et al 2003). Ubc9 and SUMO-1 were highly expressed in human premalignant conditions in response to low-grade, longterm genotoxic stress, implying that upregulation of sumoylation may be an adaptive process to genotoxic stress (Romanenko et al 2006). Furthermore, Ubc9 is overexpressed in several malignancies, such as lung adenocarcinoma (McDoniels-Silvers et al 2002), ovarian carcinoma , and melanoma .…”

Section: Potential Role Of Ubc9 In Cancermentioning

confidence: 99%

Role of SUMO/Ubc9 in DNA Damage Repair and Tumorigenesis

Moschos

2006

J Mol Hist

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DNA damage repair is an important cell function for genome integrity and its deregulation can lead to genomic instability and development of malignancies. Sumoylation is an increasingly important ubiquitin-like modification of proteins affecting protein stability, enzymatic activity, nucleocytoplasmic trafficking, and protein-protein interactions. In particular, several important DNA repair enzymes are subject to sumoylation, which appears to play a role in copping with DNA damage insults. Recent reports indicate that Ubc9, the single SUMO E2 enzyme catalyzing the conjugation of SUMO to target proteins, is overexpressed in certain tumors, such as lung adenocarcinoma, ovarian carcinoma and melanoma, suggestive of its clinic significance. This review summarizes the most important DNA damage repair pathways which are potentially affected by Ubc9/SUMO and their role in regulating the function of several proteins involved in the DNA damage repair machinery.

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“…Such a high prevalence of severe dysplasia and CIS in randomly selected BPH cases is obviously unrealistic and indicative of false-positivity. Radiation doses resulting from activity concentration of 137Cs in urine (6.47 Bq/l in the most exposed group [43,44]) were discussed previously [47]: the doses were obviously too low to cause any increase in bladder malignancy.…”

Section: Introductionmentioning

confidence: 99%

“…Diagnostic uncertainty is an apparent explanation for the fact that in different groups of males with benign prostatic hyperplasia (BPH) and females with chronic cystitis, from contaminated areas and Kiev, severe urothelial dysplasia and carcinoma in situ (CIS) were found by bladder biopsy as frequently as in 56-92 % of all randomly selected cases; while the random selection mode was repeatedly pointed out [42][43][44][45][46]. Such a high prevalence of severe dysplasia and CIS in randomly selected BPH cases is obviously unrealistic and indicative of false-positivity.…”

Section: Introductionmentioning

confidence: 99%

“…It should be stressed that overdiagnosis of premalignant and malignant bladder lesions entails overtreatment and overmanipulation including cystoscopies and repeated biopsies [42][43][44][45][46], which could have been conductive to a transmission of infection such as viral hepatitis [48,49]. It seems to be probable that the so-called "irradiation cystitis" [44,50], characterized not only by urothelial dysplasia and CIS but also by "reactive epithelial proliferation associated with hemorrhage, fibrin deposits, fibrinoid vascular changes, and multinuclear stromal cells" [50], was at least in part caused by repeated cystoscopies, biopsies, electrocoagulation etc.…”

Section: Introductionmentioning

confidence: 99%

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Malignancies after Chernobyl Accident: What Is True and What Is Untrue

Jargin¹

2016

Diagn Pathol Open

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Several publications in the field of pathology, overestimating medical consequences of the Chernobyl nuclear accident, are reviewed here. Among the causes of high registered incidence of pediatric thyroid cancer after the accident was the screening effect with detection of advanced cases. This explains also for the relatively high prevalence of dedifferentiated histological patterns and pronounced invasiveness described as the features of Chernobyl-related thyroid cancer. Mechanisms of false-positive diagnostics of thyroid and urinary bladder lesions are analyzed here. Morphological features of renal cell carcinoma from Chernobyl and adjacent areas are discussed in relation to the averagely late detection of malignancies. In conclusion, results of some molecular-genetic and other studies based on Chernobyl material should be re-evaluated, considering that many tumors detected during the first decade after the accident by the screening or brought from non-contaminated areas were advanced tumors, some of them misinterpreted as aggressive radiogenic cancers developing after a short latency.

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Involvement of Ubiquitination and Sumoylation in Bladder Lesions Induced by Persistent Long-Term Low Dose Ionizing Radiation in Humans

Cited by 25 publications

References 15 publications

Alterations of ubiquitylation and sumoylation in conventional renal cell carcinomas after the Chernobyl accident: a comparison with Spanish cases

Alterations of ubiquitylation and sumoylation in conventional renal cell carcinomas after the Chernobyl accident: a comparison with Spanish cases

Role of SUMO/Ubc9 in DNA Damage Repair and Tumorigenesis

Malignancies after Chernobyl Accident: What Is True and What Is Untrue

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