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• W2076809631 abstract "Abstract Aberrant activation of Wnts is common in human cancers, including prostate. Hypermethylation associated transcriptional silencing of Wnt antagonist genes SFRPs (Secreted Frizzled‐Related Proteins) is a frequent oncogenic event. The significance of this is not known in prostate cancer. The objectives of our study were to ( i ) profile Wnt signaling related gene expression and ( ii ) investigate methylation of Wnt antagonist genes in prostate cancer. Using TaqMan Low Density Arrays, we identified 15 Wnt signaling related genes with significantly altered expression in prostate cancer; the majority of which were upregulated in tumors. Notably, histologically benign tissue from men with prostate cancer appeared more similar to tumor ( r = 0.76) than to benign prostatic hyperplasia (BPH; r = 0.57, p < 0.001). Overall, the expression profile was highly similar between tumors of high (≥ 7) and low (≤ 6) Gleason scores. Pharmacological demethylation of PC‐3 cells with 5‐Aza‐CdR reactivated 39 genes (≥ 2‐fold); 40% of which inhibit Wnt signaling. Methylation frequencies in prostate cancer were 10% (2/20) ( SFRP1 ), 64.86% (48/74) ( SFRP2 ), 0% (0/20) ( SFRP4 ) and 60% (12/20) ( SFRP5 ). SFRP2 methylation was detected at significantly lower frequencies in high‐grade prostatic intraepithelial neoplasia (HGPIN; 30%, (6/20), p = 0.0096), tumor adjacent benign areas (8.82%, (7/69), p < 0.0001) and BPH (11.43% (4/35), p < 0.0001). The quantitative level of SFRP2 methylation (normalized index of methylation) was also significantly higher in tumors (116) than in the other samples (HGPIN = 7.45, HB = 0.47, and BPH = 0.12). We show that SFRP2 hypermethylation is a common event in prostate cancer. SFRP2 methylation in combination with other epigenetic markers may be a useful biomarker of prostate cancer." @default.
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• W2076809631 date "2012-09-28" @default.
• W2076809631 modified "2023-10-18" @default.
• W2076809631 title "Gene expression and epigenetic discovery screen reveal methylation of SFRP2 in prostate cancer" @default.
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• W2076809631 doi "https://doi.org/10.1002/ijc.27798" @default.
• W2076809631 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7560947" @default.
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• W2076809631 hasPublicationYear "2012" @default.
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