Expression and aberrant promoter methylation of Wnt inhibitory factor-1 in human astrocytomas

被引：30
作者：
Yang, Zhuanyi [1 ]
Wang, Ying [2 ]
Fang, Jiasheng [1 ]
Chen, Fenghua [1 ]
Liu, Jinfang [1 ]
Wu, Jun [1 ]
Wang, Yanjin [1 ]
机构：
[1] Cent S Univ, Xiangya Hosp, Dept Neurosurg, Changsha 410078, Hunan, Peoples R China
[2] Cent S Univ, Basic Med Sch, Dept Pathol, Changsha 410078, Hunan, Peoples R China
来源：
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH | 2010年 / 29卷
基金：
中国国家自然科学基金;
关键词：
EPIGENETIC INACTIVATION; MALIGNANT GLIOMAS; SIGNALING PATHWAY; BETA-CATENIN; CANCER; ACTIVATION; WIF-1; LUNG;
D O I：
10.1186/1756-9966-29-26
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Background: Wnt inhibitory factor-1(WIF-1) acts as a Wnt-antagonists and tumor suppressor, but hypermethylation of WIF-1 gene promoter and low expression activate Wnt signaling aberrantly and induce the development of various human tumors. With this work we intended to investigate the expression and promoter methylation status of WIF-1 gene in human astrocytomas. Methods: The tissue samples consisted of 53 astrocytomas and 6 normal brain tissues. The expression levels of WIF-1 were determined by immunohistochemistry and semiquantitative RT-PCR. The results were analyzed in correlation with clinicopathological data. Methylation status of WIF-1 gene promoter was investigated using methylation specific PCR. The relationship between methylation and expression of the genes was analyzed. Results: The average expression levels of WIF-1 protein and mRNA in astrocytomas were decreased significantly compared with normal control tissues. The protein and mRNA expression of WIF-1 gene in astrocytomas was decreased with the increase of pathological grade. Furthermore, WIF-1 promoter methylation was observed by MS-PCR in astrocytomas which showed significant reduction of WIF-1 expression. The WIF-1 promoter hypermethylation was associated with reduced expression of WIF-1 expression. Conclusion: Our results demonstrate that the WIF-1 gene is frequently down-regulated or silenced in astrocytomas by aberrant promoter methylation. This may be an important mechanism in astrocytoma carcinogenesis.
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页数：7
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