Epigenetic regulation of Wnt signaling pathway in urological cancer

• Type: Article in International Scientific Journal
• Date: 2010

Authors

Costa, VL (Author) Other; henrique, rmf (Author) ICBAS; Ribeiro, FR (Author) Other; Carvalho, JR (Author) Other; Oliveira, J (Author) Other; Lobo, F (Author) Other; Manuel R Teixeira (Author) ICBAS; Carmen Jeronimo (Author) ICBAS

Journal

Title: Epigenetics

Vol. 5

Pages: 343-351

ISSN: 1559-2294

Publisher: Taylor & Francis

Indexing

ISI Web of Knowledge - 34 Citations

Scopus - 35 Citations

Other information

Authenticus ID: P-003-6PM

DOI: 10.4161/epi.5.4.11749

Abstract (EN): Constitutive activation of the Wnt signaling pathway is a common feature of solid tumors and contributes to uncontrolled cell-growth and impaired differentiation. We hypothesized that gene silencing mediated through aberrant promoter methylation of upstream Wnt antagonist genes might result in beta-catenin accumulation, resulting in constitutive Wnt activation. Wnt antagonist genes (SFRP1, WIF1, APC and CDH1) and CTNNB1 promoter methylation was examined in genomic DNA extracted from 12 urological cancer cell lines and correlated with CTNNB1 mRNA expression. Promoter methylation status was then assessed in 36 BCa, 30 PCPCa, 31 RCT, and normal bladder mucosa (15), prostate (10) and renal (5) tissue samples. Finally, CTNNB1 mRNA relative expression levels were correlated with Wnt antagonist gene methylation status in RCT. Methylation was found in at least one Wnt antagonist gene and the CTNNB1 promoter was unmethylated in all cancer cell lines tested. When gene methylation levels were compared between cancer cell lines with high and low CTNNB1 mRNA expression, a trend was found for increased CDH1 promoter methylation levels in the former. BCa and PCPCa tumors demonstrated high frequency of promoter methylation at all tested genes. In RCT, CTNNB1 was unmethylated in all cases and the overall frequency of promoter methylation at the remainder genes was lower. Interestingly, median CTNNB1 mRNA expression levels were significantly higher in RCTs methylated in at least one Wnt antagonist gene promoter. We concluded that epigenetic deregulation of Wnt pathway inhibitors may contribute to aberrant activation of Wnt signaling pathway in bladder, prostate and renal tumors.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9