Aberrant methylation of the vascular endothelial growth factor receptor‐1 gene in prostate cancer

• Published in: Cancer science 2003-06, Vol.94 (6), p.536-539
• Main Authors: Yamada, Yasushi, Watanabe, Masatoshi, Yamanaka, Mikio, Hirokawa, Yoshifumi, Suzuki, Hiroyoshi, Takagi, Akimitsu, Matsuzaki, Takeshi, Sugimura, Yoshiki, Yatani, Ryuichi, Shiraishi, Taizo
• Format: Article
• Language: English
• Subjects: Antimetabolites, Antineoplastic - pharmacology; Azacitidine - analogs & derivatives; Azacitidine - pharmacology; Biological and medical sciences; Bisulfite; Carcinogenesis; Decitabine; DNA Methylation; DNA microarrays; Enzyme Inhibitors - pharmacology; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic - drug effects; Gene silencing; Histone deacetylase; Histone Deacetylase Inhibitors; Humans; Hydroxamic Acids - pharmacology; Male; Medical sciences; Methyltransferase; Nephrology. Urinary tract diseases; Oligonucleotide Array Sequence Analysis; Polymerase Chain Reaction; Promoter Regions, Genetic; Prostate cancer; Prostatic Hyperplasia - genetics; Prostatic Hyperplasia - pathology; Prostatic Neoplasms - genetics; Prostatic Neoplasms - pathology; Sulfites; Tumor cell lines; Tumor Cells, Cultured; Tumors of the urinary system; Urinary tract. Prostate gland; Vascular endothelial growth factor; Vascular Endothelial Growth Factor Receptor-1 - genetics; Vascular endothelial growth factor receptors
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/j.1349-7006.2003.tb01479.x

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.