The INK4a /ARF locus: role in cell cycle control for renal cell epithelial tumor growth after the Chernobyl accident
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 suppres...
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| Veröffentlicht in: | Virchows Archiv : an international journal of pathology 2004-09, Vol.445 (3), p.298-304 |
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| creator | Romanenko, Alina Morell-Quadreny, Luisa Lopez-Guerrero, Jose Antonio Pellin, Antonio Nepomnyaschy, Valentin Vozianov, Alexander Llombart-Bosch, Antonio |
| description | 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. |
| doi_str_mv | 10.1007/s00428-004-1056-7 |
| format | Article |
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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.</description><identifier>ISSN: 0945-6317</identifier><identifier>EISSN: 1432-2307</identifier><identifier>DOI: 10.1007/s00428-004-1056-7</identifier><identifier>PMID: 15232742</identifier><language>eng</language><publisher>Germany: Springer Nature B.V</publisher><subject>Adult ; Aged ; Cancer ; Carcinoma, Renal Cell - genetics ; Carcinoma, Renal Cell - metabolism ; Carcinoma, Renal Cell - pathology ; Cell Cycle - genetics ; Cell Cycle - radiation effects ; Cesium ; Cesium Isotopes - urine ; Cyclin-Dependent Kinase Inhibitor p16 - genetics ; Cyclin-Dependent Kinase Inhibitor p16 - radiation effects ; DNA Methylation ; Female ; Genes, p16 - radiation effects ; Humans ; Immunohistochemistry ; Kidney Neoplasms - genetics ; Kidney Neoplasms - metabolism ; Kidney Neoplasms - pathology ; Male ; Middle Aged ; Mutation ; Neoplasms, Radiation-Induced - genetics ; Neoplasms, Radiation-Induced - pathology ; Nuclear accidents & safety ; Nuclear power plants ; p38 Mitogen-Activated Protein Kinases - metabolism ; Polymerase Chain Reaction ; Radioactive fallout ; Tumor Suppressor Protein p14ARF - genetics ; Tumor Suppressor Protein p14ARF - radiation effects ; Ukraine</subject><ispartof>Virchows Archiv : an international journal of pathology, 2004-09, Vol.445 (3), p.298-304</ispartof><rights>Springer-Verlag 2004</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c324t-84ca66afa809bb6b2877a982790f7f42927779bfedf85e0ad60becb63ac89d2d3</citedby><cites>FETCH-LOGICAL-c324t-84ca66afa809bb6b2877a982790f7f42927779bfedf85e0ad60becb63ac89d2d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,778,782,27907,27908</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15232742$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Romanenko, Alina</creatorcontrib><creatorcontrib>Morell-Quadreny, Luisa</creatorcontrib><creatorcontrib>Lopez-Guerrero, Jose Antonio</creatorcontrib><creatorcontrib>Pellin, Antonio</creatorcontrib><creatorcontrib>Nepomnyaschy, Valentin</creatorcontrib><creatorcontrib>Vozianov, Alexander</creatorcontrib><creatorcontrib>Llombart-Bosch, Antonio</creatorcontrib><title>The INK4a /ARF locus: role in cell cycle control for renal cell epithelial tumor growth after the Chernobyl accident</title><title>Virchows Archiv : an international journal of pathology</title><addtitle>Virchows Arch</addtitle><description>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. 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These actions could lead to disruptions and loss of cell cycle checkpoints and, thereby, to cellular transformation.</description><subject>Adult</subject><subject>Aged</subject><subject>Cancer</subject><subject>Carcinoma, Renal Cell - genetics</subject><subject>Carcinoma, Renal Cell - metabolism</subject><subject>Carcinoma, Renal Cell - pathology</subject><subject>Cell Cycle - genetics</subject><subject>Cell Cycle - radiation effects</subject><subject>Cesium</subject><subject>Cesium Isotopes - urine</subject><subject>Cyclin-Dependent Kinase Inhibitor p16 - genetics</subject><subject>Cyclin-Dependent Kinase Inhibitor p16 - radiation effects</subject><subject>DNA Methylation</subject><subject>Female</subject><subject>Genes, p16 - radiation effects</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Kidney Neoplasms - genetics</subject><subject>Kidney Neoplasms - metabolism</subject><subject>Kidney Neoplasms - pathology</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>Neoplasms, Radiation-Induced - genetics</subject><subject>Neoplasms, Radiation-Induced - pathology</subject><subject>Nuclear accidents & safety</subject><subject>Nuclear power plants</subject><subject>p38 Mitogen-Activated Protein Kinases - metabolism</subject><subject>Polymerase Chain Reaction</subject><subject>Radioactive fallout</subject><subject>Tumor Suppressor Protein p14ARF - genetics</subject><subject>Tumor Suppressor Protein p14ARF - radiation effects</subject><subject>Ukraine</subject><issn>0945-6317</issn><issn>1432-2307</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNpFUE1LAzEQDaLYWv0BXiR4X51ks0nWmxSrRVGQeg7ZbGJXtpuaZJH-eyMteHnDzPtgeAhdErghAOI2AjAqi4wFgYoX4ghNCStpQUsQx2gKNasKXhIxQWcxfgFQIgk_RRNS0ZIKRqcordYWL1-fmca39-8L3HszxjscfG9xN2Bj-x6bncmb8UPKZ-x8wMEOut-Tdtulte27vKdxk7nP4H_SGmuXbMCZwvO1DYNvdj3WxnStHdI5OnG6j_biMGfoY_Gwmj8VL2-Py_n9S2FKylIhmdGca6cl1E3DGyqF0LWkogYnHKM1FULUjbOtk5UF3XJorGl4qY2sW9qWM3S9z90G_z3amNSXH0N-PSpJQXAggmUR2YtM8DEG69Q2dBsddoqA-qtZ7WtWGdVfzUpkz9UheGw2tv13HHotfwFuP3g9</recordid><startdate>200409</startdate><enddate>200409</enddate><creator>Romanenko, Alina</creator><creator>Morell-Quadreny, Luisa</creator><creator>Lopez-Guerrero, Jose Antonio</creator><creator>Pellin, Antonio</creator><creator>Nepomnyaschy, Valentin</creator><creator>Vozianov, Alexander</creator><creator>Llombart-Bosch, Antonio</creator><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7T5</scope><scope>7T7</scope><scope>7TM</scope><scope>7TO</scope><scope>7U7</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope></search><sort><creationdate>200409</creationdate><title>The INK4a /ARF locus: role in cell cycle control for renal cell epithelial tumor growth after the Chernobyl accident</title><author>Romanenko, Alina ; Morell-Quadreny, Luisa ; Lopez-Guerrero, Jose Antonio ; Pellin, Antonio ; Nepomnyaschy, Valentin ; Vozianov, Alexander ; Llombart-Bosch, Antonio</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c324t-84ca66afa809bb6b2877a982790f7f42927779bfedf85e0ad60becb63ac89d2d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Cancer</topic><topic>Carcinoma, Renal Cell - 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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.</abstract><cop>Germany</cop><pub>Springer Nature B.V</pub><pmid>15232742</pmid><doi>10.1007/s00428-004-1056-7</doi><tpages>7</tpages></addata></record> |
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| subjects | Adult Aged Cancer Carcinoma, Renal Cell - genetics Carcinoma, Renal Cell - metabolism Carcinoma, Renal Cell - pathology Cell Cycle - genetics Cell Cycle - radiation effects Cesium Cesium Isotopes - urine Cyclin-Dependent Kinase Inhibitor p16 - genetics Cyclin-Dependent Kinase Inhibitor p16 - radiation effects DNA Methylation Female Genes, p16 - radiation effects Humans Immunohistochemistry Kidney Neoplasms - genetics Kidney Neoplasms - metabolism Kidney Neoplasms - pathology Male Middle Aged Mutation Neoplasms, Radiation-Induced - genetics Neoplasms, Radiation-Induced - pathology Nuclear accidents & safety Nuclear power plants p38 Mitogen-Activated Protein Kinases - metabolism Polymerase Chain Reaction Radioactive fallout Tumor Suppressor Protein p14ARF - genetics Tumor Suppressor Protein p14ARF - radiation effects Ukraine |
| title | The INK4a /ARF locus: role in cell cycle control for renal cell epithelial tumor growth after the Chernobyl accident |
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