title: Promoter hypermethylation correlates with the Hsulf-1 silencing in human breast and gastric cancer.
abstract: The HSulf-1 gene is an important factor that modulates the sulfation status of heparan sulfate proteoglycans (HSPGs) in the extracellular matrix, resulting in disturbance of HSPG-related signal transduction pathways. Recently, HSulf-1 has been reported to be down-regulated in several human cancers. In this study, we first cloned and characterized the 5' promoter region of the HSulf-1 gene (around 400 bp) that contained high basal promoter activity. We also found that this functional promoter region was hypermethylated in a number of human cancer cell lines. Furthermore, we found that hypermethylation in this promoter region correlated with the down-regulation of the HSulf-1 expression in human breast and gastric cancer cell lines and tissue samples. These results suggest that the promoter hypermethylation may be one of the mechanisms of the HSulf-1 gene silencing in human breast and gastric cancers. Finally, we demonstrated that the HSulf-1 promoter was more frequently (p<0.05) methylated in cell-free DNA extracted from serum samples of human breast and gastric cancer patients than that of healthy people (76.2%, 55.0% and 19.0%, respectively), indicating that detection of the HSulf-1 promoter methylation in serum samples may have clinical implications in early detection and diagnosis of human breast and gastric cancers.
authors.affiliation: Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Chen
authors.forename: Jie-Qing
authors.initials: JQ
authors.lastname: Fan
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Qiu-Shi
authors.initials: QS
authors.lastname: Li
authors.forename: Zhao
authors.initials: Z
authors.lastname: Yan
authors.forename: Xue-Ke
authors.initials: XK
authors.lastname: Jia
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Liu
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Wei
authors.forename: Feng-Zhi
authors.initials: FZ
authors.lastname: Zhang
authors.forename: Hong
authors.initials: H
authors.lastname: Gao
authors.forename: Jun-Pu
authors.initials: JP
authors.lastname: Xu
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Dong
authors.forename: Jie
authors.initials: J
authors.lastname: Dai
authors.forename: Hai-Meng
authors.initials: HM
authors.lastname: Zhou
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics*; D015238:Sulfotransferases / Q000235:genetics*; D014162:Transfection
chemical_list: C470791:SULF1 protein, human; D015238:Sulfotransferases