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

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.