title: 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.
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.
authors: Brain Tumor Research Center, Beijing Neurosurgical Institute, Department of Neurosurgery, Beijing Tiantan Hospital affiliated to Capital Medical University, Beijing 100050, PR China.
authors: Yiqiang
authors: Y
authors: Zhou
authors: Brain Tumor Research Center, Beijing Neurosurgical Institute, Department of Neurosurgery, Beijing Tiantan Hospital affiliated to Capital Medical University, Beijing 100050, PR China.
authors: Guishan
authors: G
authors: Jin
authors: Brain Tumor Research Center, Beijing Neurosurgical Institute, Department of Neurosurgery, Beijing Tiantan Hospital affiliated to Capital Medical University, Beijing 100050, PR China.
authors: Ruifang
authors: R
authors: Mi
authors: Brain Tumor Research Center, Beijing Neurosurgical Institute, Department of Neurosurgery, Beijing Tiantan Hospital affiliated to Capital Medical University, Beijing 100050, PR China.
authors: Chengyuan
authors: C
authors: Dong
authors: Brain Tumor Research Center, Beijing Neurosurgical Institute, Department of Neurosurgery, Beijing Tiantan Hospital affiliated to Capital Medical University, Beijing 100050, PR China.
authors: Jin
authors: J
authors: Zhang
authors: 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.
authors: Fusheng
authors: F
authors: Liu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002648:Child; D019175:DNA Methylation / Q000187:drug effects; D005260:Female; D005492:Folic Acid / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005910:Glioma / Q000188:drug therapy; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics; D020574:Proto-Oncogene Proteins c-sis / Q000235:genetics / Q000378:metabolism*; D014803:Vitamin B Complex / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D019394:Ki-67 Antigen; D020574:Proto-Oncogene Proteins c-sis; D014803:Vitamin B Complex; D005492:Folic Acid
keywords: 5-aza-dC; Folate; Gene methylation; Glioma; PDGF-B