期刊
CANCER BIOLOGY & THERAPY
卷 4, 期 1, 页码 70-76出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/cbt.4.1.1378
关键词
chemokine receptor; CXCR4; methylation; pancreatic cancer
类别
资金
- NATIONAL CANCER INSTITUTE [P50CA062924] Funding Source: NIH RePORTER
- NCI NIH HHS [CA62924] Funding Source: Medline
Despite the biological and clinical importance of the interaction between the chemokine receptor CXCR4 and its ligand CXCL12 (SDF-1 alpha) in human cancers, little is known about transcriptional regulation of the CXCR,4 gene. Although aberrant hypermethylation in cancer has been described typically in genes with tumor-suppressor properties, this epigenetic alteration has also been observed to affect potential cancer-promoting genes. We now demonstrate that DNA methylation influences CXCR4 expression in human pancreatic cancer. Gene expression profiling and reverse transcription-PCR identified a significant proportion of pancreatic cancer cell lines that displayed little or no CXCR4 mRNA expression. Using methylation-specific PCR, combined bisulfite restriction analysis, and bisulfite sequencing, we found the 5' CpG islands of the CXCR4 gene to be unmethylated in normal pancreas, whereas promoter hypermethylation was detected in 45% (9 of 20) of pancreatic cancer cell lines and in 46% (46 of 100) of primary pancreatic adenocarcinomas. There was a significant inverse correlation between methylation and mRNA expression level of CXCR4 (P = 0.008) in a large panel of pancreatic cancer cell lines. Constitutive as well as inducible expression of CXCR,4 could be restored in methylated cell lines pharmacologically using epigenetic modifying drugs. These findings demonstrate the first evidence for epigenetic regulation of CXCR4 in human cancers, providing new insights into the role of CXCR4/CXCL12 interactions in tumor progression.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据