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No evidence for DNA methylation of von Hippel-Lindau ubiquitin ligase complex genes in breast cancer

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Abstract

pVHL is the central component of an ubiquitin ligase complex that targets hypoxia-inducible factor 1α (HIF-1α) for proteasomal degradation. This complex includes four other genes, Cullin 2 (CUL2), elongin C (TCEB1), elongin B (TCEB2) and ring-box 1 (RBX1). VHL has previously been reported to be methylated in sporadic renal cell carcinoma. Since HIF-1α is frequently expressed in breast carcinomas, we evaluated DNA methylation as a possible mechanism of silencing one or more of the VHL complex genes. Methylation-specific high resolution melting (MS-HRM) was used to screen the proximal promoter CpG islands for methylation of the VHL ubiquitin ligase complex genes. We were unable to identify methylation of any of the five genes in 84 breast carcinoma samples or in a range of cancer cell lines including 13 breast cancer cell lines of various subtypes. We were able, however, to identify VHL methylation in control renal cell carcinoma samples. Epigenetic silencing by promoter DNA methylation for VHL and the complex genes, CUL2, elongin C (TCEB1), elongin B (TCEB2) and RBX1, is unlikely to play a role in HIF-1α upregulation in breast carcinomas.

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References

  1. Cockman ME, Masson N, Mole DR et al (2000) Hypoxia inducible factor-alpha binding and ubiquitylation by the von Hippel-Lindau tumor suppressor protein. J Biol Chem 275(33):25733–25741

    Article  CAS  PubMed  Google Scholar 

  2. Harris AL (2002) Hypoxia—a key regulatory factor in tumour growth. Nat Rev Cancer 2(1):38–47

    Article  CAS  PubMed  Google Scholar 

  3. Semenza GL (2003) Targeting HIF-1 for cancer therapy. Nat Rev Cancer 3(10):721–732

    Article  CAS  PubMed  Google Scholar 

  4. Banks RE, Tirukonda P, Taylor C et al (2006) Genetic and epigenetic analysis of von Hippel-Lindau (VHL) gene alterations and relationship with clinical variables in sporadic renal cancer. Cancer Res 66(4):2000–2011

    Article  CAS  PubMed  Google Scholar 

  5. Patard JJ, Rioux-Leclercq N, Masson D et al (2009) Absence of VHL gene alteration and high VEGF expression are associated with tumour aggressiveness and poor survival of renal-cell carcinoma. Br J Cancer 101(8):1417–1424

    Article  CAS  PubMed  Google Scholar 

  6. Herman JG, Latif F, Weng Y et al (1994) Silencing of the VHL tumor-suppressor gene by DNA methylation in renal carcinoma. Proc Natl Acad Sci USA 91(21):9700–9704

    Article  CAS  PubMed  Google Scholar 

  7. Hatzimichael E, Dranitsaris G, Dasoula A et al (2009) Von Hippel-Lindau methylation status in patients with multiple myeloma: a potential predictive factor for the development of bone disease. Clin Lymphoma Myeloma 9(3):239–242

    Article  CAS  PubMed  Google Scholar 

  8. Wojdacz TK, Dobrovic A (2007) Methylation-sensitive high resolution melting (MS-HRM): a new approach for sensitive and high-throughput assessment of methylation. Nucl Acids Res 35(6):e41

    Google Scholar 

  9. Sourvinos G, Miyakis S, Liloglou TL et al (2001) Von Hippel-Lindau tumour suppressor gene is not involved in sporadic human breast cancer. Tumour Biol 22(3):131–136

    Article  CAS  PubMed  Google Scholar 

  10. Zia MK, Rmali KA, Watkins G et al (2007) The expression of the von Hippel-Lindau gene product and its impact on invasiveness of human breast cancer cells. Int J Mol Med 20(4):605–611

    CAS  PubMed  Google Scholar 

  11. Park SW, Chung NG, Hur SY et al (2009) Mutational analysis of hypoxia-related genes HIF1alpha and CUL2 in common human cancers. APMIS 117(12):880–885

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work is supported by the Victorian Breast Cancer Research Consortium, Australia, the Cancer Council of Victoria and the National Breast Cancer Foundation. We would like to thank Professor Adrian L. Harris, University of Oxford, UK for the kind donation of breast tumour DNA.

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Correspondence to Stephen B. Fox.

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Huang, K.T., Dobrovic, A. & Fox, S.B. No evidence for DNA methylation of von Hippel-Lindau ubiquitin ligase complex genes in breast cancer. Breast Cancer Res Treat 124, 853–856 (2010). https://doi.org/10.1007/s10549-010-1087-5

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  • DOI: https://doi.org/10.1007/s10549-010-1087-5

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