RGD Reference Report - Phosphatase and tensin homolog in cerebral cavernous malformation: a potential role in pathological angiogenesis. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Phosphatase and tensin homolog in cerebral cavernous malformation: a potential role in pathological angiogenesis.

Authors: Zhu, Yuan  Peters, Christian  Hallier-Neelsen, Monika  Miller, Dorothea  Pagenstecher, Axel  Bertalanffy, Helmut  Sure, Ulrich 
Citation: Zhu Y, etal., J Neurosurg. 2009 Mar;110(3):530-9. doi: 10.3171/2008.7.17626.
RGD ID: 12859036
Pubmed: (View Article at PubMed) PMID:19061355
DOI: Full-text: DOI:10.3171/2008.7.17626


OBJECT: Cerebral cavernous malformations (CCMs) are the most common vascular malformation of the central nervous system and involve dysregulated angiogenesis. However, the underlying mechanism of this disease is poorly understood. Phosphatase and tensin homolog (PTEN) plays a crucial role in regulating angiogenesis. The authors attempted to determine whether PTEN is involved in the pathological angiogenesis of CCM.
METHODS: The authors used Western blot analysis and immunohistochemical methods to detect the expression of PTEN, PCNA, and P-Akt in the surgical specimens of CCMs and controls. The function of PTEN in cell proliferation was studied after PTEN silencing in endothelial cultures by using the short interfering RNA technique.
RESULTS: Western blot analysis showed significant reduction of PTEN protein expression in CCMs compared with control brain tissue (p < 0.01). Immunohistochemical analysis confirmed PTEN insufficiency in 33% of vascular endothelia of CCMs, which was significantly higher than that of controls (2%, p < 0.01). Furthermore, PTEN insufficiency occurred more frequently in multiple CCMs (44%) and in small lesions (39%) than in single CCMs (28%, p < 0.05) and large lesions (30%, p < 0.05), respectively, suggesting a potential role of PTEN in the progression of the lesions. Of note, a negative correlation was observed between the expression of PTEN and PCNA in CCM endothelial cells. However, Akt was not constitutively activated in CCMs. Using cultured endothelial cells, the authors demonstrated that PTEN silencing by short interfering RNA increased Akt activation, PCNA expression, and cell proliferation (p < 0.001). Surprisingly, the PTEN silencing-mediated increase in endothelial proliferation was not reversed by the PI3K inhibitor wortmannin.
CONCLUSIONS: In this study, the authors report for the first time a significant PTEN insufficiency in CCM vessels associated with endothelial proliferation. The in vitro study provides direct evidence for a pivotal role of PTEN in regulating endothelial proliferation, most likely through a PI3K-independent pathway. The authors suggest that PTEN insufficiency is potentially involved in CCM by stimulating angiogenesis.

Annotation

Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Pten  (phosphatase and tensin homolog)

Genes (Mus musculus)
Pten  (phosphatase and tensin homolog)

Genes (Homo sapiens)
PTEN  (phosphatase and tensin homolog)


Additional Information