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Brain Res. 2014 Mar 27;1556:57-66. doi: 10.1016/j.brainres.2014.01.045. Epub 2014 Feb 3.

The methylation status of the platelet-derived growth factor-B gene promoter and its regulation of cellular proliferation following folate treatment in human glioma cells.

Author information

1
Brain Tumor Research Center, Beijing Neurosurgical Institute, Department of Neurosurgery, Beijing Tiantan Hospital affiliated to Capital Medical University, Beijing 100050, PR China.
2
Brain Tumor Research Center, Beijing Neurosurgical Institute, Department of Neurosurgery, Beijing Tiantan Hospital affiliated to Capital Medical University, Beijing 100050, PR China. Electronic address: liufushengs@hotmail.com.

Abstract

Platelet-derived growth factor-B (PDGF-B) is a growth factor that regulates cell migration, proliferation, and differentiation, and is involved in several physical and pathological processes. The overexpression of PDGF-B in glioma surgical samples revealed its effect on tumorigenesis. In this study, we determined that the expression of PDGF-B in 54 glioma samples varied among different grades and was correlated with the cell proliferation marker, Ki-67. Using pyrosequencing, we quantitatively assessed PDGF-B gene methylation levels and determined that hypomethylation promotes increased expression of PDGF-B in higher grade gliomas. Furthermore, we treated two glioma cell lines with a demethylating agent (5-aza-2'-deoxycitidine, 5-aza-dC) or a remethylating agent (folate) to alter the methylation status of PDGF-B. The epigenetic regulation of the PDGF-B gene not only modulated the expression levels of PDGF-B but also affected the cellular proliferation induced by TGFβ-Smad activity and the PDGF-B peptide itself. Our work showed the importance of the methylation status of the PDGF-B gene promoter, and suggests that the epigenetic regulation of the PDGF-B gene may serve as a potential therapeutic target for the inhibition of glioma proliferation.

KEYWORDS:

5-aza-dC; Folate; Gene methylation; Glioma; PDGF-B

PMID:
24502980
DOI:
10.1016/j.brainres.2014.01.045
[Indexed for MEDLINE]
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