Open AccessAberrant methylation of the vascular endothelial growth factor receptor‐1 gene in prostate cancer
Author(s) -
Yamada Yasushi,
Watanabe Masatoshi,
Yamanaka Mikio,
Hirokawa Yoshifumi,
Suzuki Hiroyoshi,
Takagi Akimitsu,
Matsuzaki Takeshi,
Sugimura Yoshiki,
Yatani Ryuichi,
Shiraishi Taizo
Publication year - 2003
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2003.tb01479.x
Subject(s) - du145 , prostate cancer , dna methylation , cancer research , lncap , bisulfite sequencing , biology , methylation , cancer , carcinogenesis , pca3 , vascular endothelial growth factor , microbiology and biotechnology , epigenetics , prostate , gene expression , gene , genetics , vegf receptors
Transcriptional silencing of cancer‐related genes by DNA methylation is observed in various cancers. To identify genes controlled by methylation in prostate cancer, we used cDNA microarray analysis to investigate gene expression in prostate cancer cell lines LNCaP and DU145 treated with a methyltransferase inhibitor alone or together with a histone deacetylase inhibitor. We detected significant changes (3.4–5.7%) in gene expression in prostate cancer cell lines with the drug treatments. Among the affected genes, that for the vascular endothelial growth factor receptor 1 ( VEGFR‐1 ) was re‐expressed in LNCaP and DU145 after the drug treatments. Bisulfite sequencing revealed the promoter and exon 1 of the VEGFR‐1 to be hypermethylated in the cell lines. These results support the idea that methylation is associated with loss of VEGFR‐1 mRNA expression in prostate cancer cell lines. Combined bisulfite restriction analysis (COBRA) showed the gene to be methylated in 24 (38.1%) of 63 primary local prostate cancer samples, while in all 13 benign prostate samples it was not. These findings indicate that methylation of VEGFR‐1 is related with prostatic carcinogenesis.