Involvement of PTEN promoter methylation in cerebral cavernous malformations

  • Zhu Y
  • Wloch A
  • Wu Q
 et al. 
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Abstract

Background and Purpose-- Cerebral cavernous malformations (CCMs) are prevalent cerebral vascular lesions involving aberrant angiogenesis. However, the underlying mechanism is poorly understood. Phosphatase and tension homolog deleted on chromosome 10 (PTEN), a tumor suppressor, is frequently deficient in various pathologies due to mutation or epigenetic alterations. PTEN promoter hypermethylation is a major epigenetic silencing mechanism leading to activation of angiogenesis in tumors. The present study aimed to investigate whether PTEN promoter methylation was involved in CCMs. Methods-- PTEN promoter methylation was detected in surgical specimens of CCMs (n=69) by methylation-specific polymerase chain reaction. The methylation status was correlated to the clinical manifestations and to PTEN expression, which was analyzed by both Western blot and immunohistochemistry. To investigate the endothelial proliferation and the potential signaling pathways affected by PTEN methylation, proliferating cell nuclear antigen as well as phosphor-Akt and phosphor-Erk1,2 were detected by immunofluorescence and Western blot, respectively, in CCM specimens. Results-- Methylation-specific polymerase chain reaction revealed PTEN promoter methylation in 15.9% CCMs. Strikingly, 5 of 6 familial CCMs showed PTEN promoter methylation (83.3%), which was significantly higher than in sporadic cases (9.4%; P

Author-supplied keywords

  • Cerebral cavernous malformation
  • Endothelial proliferation
  • Erkl,2 activation
  • PTEN downregulation
  • PTEN promoter methylation

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Authors

  • Yuan Zhu

  • Andreas Wloch

  • Qun Wu

  • Christian Peters

  • Axel Pagenstecher

  • Helmut Bertalanffy

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