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Promoter hypermethylation correlates with the Hsulf-1 silencing in human breast and gastric cancer

✍ Scribed by Zhao Chen; Jie-Qing Fan; Jie Li; Qiu-Shi Li; Zhao Yan; Xue-Ke Jia; Wei-Dong Liu; Li-Jun Wei; Feng-Zhi Zhang; Hong Gao; Jun-Pu Xu; Xiao-Ming Dong; Jie Dai; Hai-Meng Zhou

Publisher
John Wiley and Sons
Year
2009
Tongue
French
Weight
326 KB
Volume
124
Category
Article
ISSN
0020-7136

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✦ Synopsis

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. © 2008 Wiley‐Liss, Inc.

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