E-Cadherin Downregulation is Mediated by Promoter Methylation in Canine Prostate Cancer.

摘要: E-cadherin is a transmembrane glycoprotein responsible for cell-to-cell adhesion, and its loss has been associated with metastasis development. Although downregulation was previously reported in canine prostate cancer (PC), the mechanism involved this process unclear. It well established that dogs, besides humans, spontaneously develop PC high frequency; therefore, an interesting model to study human PC. In PC, CDH1 methylation downregulation. However, no previous studies have described pattern of promoter Herein, we evaluated protein gene expression compared normal tissues. DNA investigated as regulatory silencing. Our cohort composed 20 prostates, proliferative inflammatory atrophy (PIA) lesions, 11 metastases from 60 dogs. The assessed by immunohistochemistry western blotting qPCR. Bisulfite- pyrosequencing assay performed investigate pattern. Membranous observed all prostatic A higher number negative cells detected more frequently PIA samples. High-grade showed diffuse membranous positive immunostaining. Furthermore, patients presented shorter survival time Gleason scores. Western qPCR assays confirmed immunohistochemical results, showing lower levels We identified hypermethylation An vitro two (PC1 PC2 cell lines) confirm expression. PC1 line after 5-Aza-dC treatment, decreased increased were observed. Positive massively found (mean 90.6%). conclusion, low protein, metastatic foci occur re-expression confirming relevance these processes.