Related Experiment Video

Updated: Jun 26, 2026

Induction and Micro-CT Imaging of Cerebral Cavernous Malformations in Mouse Model
05:12

Induction and Micro-CT Imaging of Cerebral Cavernous Malformations in Mouse Model

Published on: September 4, 2017

Involvement of PTEN promoter methylation in cerebral cavernous malformations

Yuan Zhu1, Andreas Wloch, Qun Wu

  • 1Department of Neurosurgery, University of Marburg, Marburg, Germany. yuan.zhu@uk-essen.de

Stroke
|January 2, 2009
PubMed
Abstract

Insights

PTEN promoter methylation is involved in cerebral cavernous malformations (CCMs), especially familial CCMs. This epigenetic alteration and Erk1,2 signaling may be key to CCM development and treatment.

Area of Science:

  • Neuroscience
  • Genetics
  • Oncology

Background:

  • Cerebral cavernous malformations (CCMs) are common vascular lesions in the brain.
  • The mechanisms driving CCM development, particularly aberrant angiogenesis, are not fully understood.
  • PTEN (phosphatase and tension homolog deleted on chromosome 10), a tumor suppressor, is often deficient in diseases due to epigenetic changes like promoter hypermethylation, which can activate angiogenesis.

Purpose of the Study:

  • To investigate the role of PTEN promoter methylation in the pathogenesis of CCMs.
  • To determine if PTEN promoter methylation is associated with specific clinical features of CCMs.
  • To explore the downstream signaling pathways affected by PTEN methylation in CCMs.

Main Methods:

  • PTEN promoter methylation was assessed in 69 CCM surgical specimens using methylation-specific polymerase chain reaction.
  • PTEN expression levels were analyzed via Western blot and immunohistochemistry.
  • Endothelial proliferation (proliferating cell nuclear antigen) and signaling pathway activation (phosphor-Akt, phosphor-Erk1,2) were evaluated using immunofluorescence and Western blot.

Main Results:

  • PTEN promoter methylation was detected in 15.9% of CCMs, significantly higher in familial CCMs (83.3%) than sporadic cases (9.4%).
  • Methylation was more frequent in multiple CCMs (46.7%) compared to single lesions (11.8%).
  • PTEN-methylated CCMs showed significantly reduced PTEN expression, inversely correlated with proliferating cell nuclear antigen and Erk1,2 activation.

Conclusions:

  • PTEN promoter methylation is implicated in CCM pathogenesis, particularly in familial forms, representing a novel epigenetic mechanism.
  • The study identifies Erk1,2 signaling activation in CCM lesions, suggesting its potential as a therapeutic target for this disease.

More Related Videos

A Novel Strategy Combining Array-CGH, Whole-exome Sequencing and In Utero Electroporation in Rodents to Identify Causative Genes for Brain Malformations08:22

A Novel Strategy Combining Array-CGH, Whole-exome Sequencing and In Utero Electroporation in Rodents to Identify Causative Genes for Brain Malformations

Published on: December 1, 2017

Modeling Astrocytoma Pathogenesis In Vitro and In Vivo Using Cortical Astrocytes or Neural Stem Cells from Conditional, Genetically Engineered Mice10:13

Modeling Astrocytoma Pathogenesis In Vitro and In Vivo Using Cortical Astrocytes or Neural Stem Cells from Conditional, Genetically Engineered Mice

Published on: August 12, 2014

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Epigenetic Regulation01:46

Epigenetic Regulation

Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
Epigenetic Regulation01:37

Epigenetic Regulation

Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...