Promoter hypermethylation correlates with the Hsulf-1 silencing in human breast and gastric cancer.
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.
Chen
Zhao
Z
Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing, China.
Fan
Jie-Qing
JQ
Li
Jie
J
Li
Qiu-Shi
QS
Yan
Zhao
Z
Jia
Xue-Ke
XK
Liu
Wei-Dong
WD
Wei
Li-Jun
LJ
Zhang
Feng-Zhi
FZ
Gao
Hong
H
Xu
Jun-Pu
JP
Dong
Xiao-Ming
XM
Dai
Jie
J
Zhou
Hai-Meng
HM
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
C470791:SULF1 protein, human; D015238:Sulfotransferases