Secreted frizzled-related protein-5 is epigenetically downregulated and functions as a tumor suppressor in kidney cancer
✍ Scribed by Kazumori Kawakami; Soichiro Yamamura; Hiroshi Hirata; Koji Ueno; Sharanjot Saini; Shahana Majid; Yuichiro Tanaka; Ken Kawamoto; Hideki Enokida; Masayuki Nakagawa; Rajvir Dahiya
- Book ID
- 102865184
- Publisher
- John Wiley and Sons
- Year
- 2010
- Tongue
- French
- Weight
- 592 KB
- Volume
- 128
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Abstract
Secreted frizzled‐related protein‐5 (sFRP‐5) has been identified as 1 of the secreted antagonists that bind Wnt protein. However, the functional significance of sFRP‐5 in renal cell cancer (RCC) has not been reported. We hypothesized that sFRP‐5 may be epigenetically downregulated through DNA methylation and histone modification and function as a tumor suppressor gene in RCC. Using tissue microarray and real‐time RT‐PCR, we found that sFRP‐5 was significantly downregulated in kidney cancer tissues and cell lines, respectively. DNA bisulfite sequencing of the sFRP‐5 promoter region in RCC cell lines showed it to be densely methylated, whereas there was few promoter methylation in normal kidney. The sFRP‐5 expression was restored and the acetylation of H3 and H4 histones associated with the sFRP‐5 promoter region were significantly increased after treatment with demethylation agent (5‐Aza‐dc) and histone deacetylase inhibitor (TSA). When RCC cells were transfected with the sFRP‐5 gene, significant inhibition of anchorage independent colony formation and cell invasion were observed compared to controls. The sFRP‐5 transfection also significantly induced apoptosis in RCC cells. In conclusion, this is the first report documenting that the sFRP‐5 is downregulated by promoter methylation and histone acetylation and functions as a tumor suppressor gene by inducing apoptosis in RCC cells.