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Title
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Different angiogenic potential in low and high grade sporadic clear cell renal cell carcinoma is not related to alterations in the von HippelLindau gene
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Author
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Abstract
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| Background: von HippelLindau (VHL) inactivation is common in sporadic clear cell renal cell carcinomas (ccRCC). pVHL is part of the ubiquitin ligase complex that targets the alpha subunits of hypoxia-inducible transcription factor (HIF) for degradation under well-oxygenated conditions. In the absence of wild-type pVHL, as observed in VHL patients and most sporadic ccRCCs, constitutive upregulation of HIF results in transcriptional activation of angiogenesis-related genes, such as VEGF. Differences in angiogenic activity within the group of ccRCCs were reported and strong genotype-phenotype correlations were found in patients with VHL disease, raising a question about the importance of VHL inactivation status in angiogenic behaviour and tumour progression. Methods: To address this question, we investigated the influence of VHL mutation (direct sequencing)/hypermethylation (methylation-specific PCR) on angiogenesis/tumour parameters (immunohistochemistry) in 150 patients with sporadic ccRCC. Results: We found no significant association between VHL mutation or methylation and angiogenesis/tumour parameters. Conclusion: These data indicate that tumour progression and angiogenesis are not directly influenced by VHL alterations and that additional genetic/epigenetic events should be considered to explain the diverse angiogenic and proliferative behaviour during tumour progression. |
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Language
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English
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Source (journal)
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Cellular oncology
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Publication
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2009
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ISSN
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1570-5870
1875-8606
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DOI
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10.3233/CLO-2009-0482
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Volume/pages
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31
:5
(2009)
, p. 371-382
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ISI
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000270463400005
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Full text (Publisher's DOI)
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