title: Aberrant methylation of Polo-like kinase CpG islands in Plk4 heterozygous mice.
abstract: BACKGROUND
  Hepatocellular carcinoma (HCC), one of the most common cancers world-wide occurs twice as often in men compared to women. Predisposing conditions such as alcoholism, chronic viral hepatitis, aflatoxin B1 ingestion, and cirrhosis all contribute to the development of HCC.
  
  
  METHODS
  We used a combination of methylation specific PCR and bisulfite sequencing, qReal-Time PCR (qPCR), and Western blot analysis to examine epigenetic changes for the Polo-like kinases (Plks) during the development of hepatocellular carcinoma (HCC) in Plk4 heterozygous mice and murine embryonic fibroblasts (MEFs).
  
  
  RESULTS
  Here we report that the promoter methylation of Plk4 CpG islands increases with age, was more prevalent in males and that Plk4 epigenetic modification and subsequent downregulation of expression was associated with the development of HCC in Plk4 mutant mice. Interestingly, the opposite occurs with another Plk family member, Plk1 which was typically hypermethylated in normal liver tissue but became hypomethylated and upregulated in liver tumours. Furthermore, upon alcohol exposure murine embryonic fibroblasts exhibited increased Plk4 hypermethylation and downregulation along with increased centrosome numbers and multinucleation.
  
  
  CONCLUSIONS
  These results suggest that aberrant Plk methylation is correlated with the development of HCC in mice.
authors.affiliation: Department of Biological Sciences, University of Windsor, 401 Sunset Avenue, Windsor, Ontario N9B 3P4, Canada.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Ward
authors.forename: Alan
authors.initials: A
authors.lastname: Morettin
authors.forename: David
authors.initials: D
authors.lastname: Shum
authors.forename: John W
authors.initials: JW
authors.lastname: Hudson
mesh_terms: D000375:Aging / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology; D002478:Cells, Cultured; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006579:Heterozygote; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*
chemical_list: C088051:Plk4 protein, mouse; D017346:Protein Serine-Threonine Kinases