title: Expression of phosphatidylethanolamine N-methyltransferase in human hepatocellular carcinomas.
abstract: OBJECTIVE
  Hepatic phosphatidylethanolamine is converted into phosphatidylcholine by the enzyme phosphatidylethanolamine N-methyltransferase (PEMT) when the dietary choline supply is inadequate. Our previous reports implicated PEMT in the regulation of hepatocyte growth and transformation. In the present study, we analyzed PEMT activity, PEMPT gene status and its mRNA expression in 29 human hepatocellular carcinomas (HCC).
  
  
  METHODS
  The status of the PEMPT gene and PEMT2 mRNA expression were evaluated with Southern and Northern blotting, respectively, in HCC and the noninvolved liver. PEMT activity was assessed by biochemical assay. Cell proliferation markers were defined by immunohistochemical or histoautoradiographic methods.
  
  
  RESULTS
  PEMT activity was lower in HCC than in the noninvolved liver and it was negligible in 62% of the tumors. No deletions or mutations of the PEMPT gene were found and PEMT2 mRNA expression was absent or reduced in HCC compared with peritumoral liver tissue. PEMT2 mRNA expression was inversely related to tumor proliferation and to histologic grade. Patients whose HCC did not express PEMT2 mRNA showed poorer outcomes for cancer-related survival than those with PEMT2-positive HCC.
  
  
  CONCLUSIONS
  The present findings suggest that (1). clones lacking PEMT2 expression may have been selected during liver tumorigenesis and progression, and (2). PEMT2 expression seems to be associated with clinical progression.
authors.affiliation: Department DISCAFF, University of East Piedmont 'Amedeo Avogadro', Novara, Italy. tessitore@pharm.unipmn.it
authors.forename: Luciana
authors.initials: L
authors.lastname: Tessitore
authors.forename: Barbara
authors.initials: B
authors.lastname: Marengo
authors.forename: Dennis E
authors.initials: DE
authors.lastname: Vance
authors.forename: Mauro
authors.initials: M
authors.lastname: Papotti
authors.forename: Antonio
authors.initials: A
authors.lastname: Mussa
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Daidone
authors.forename: Aurora
authors.initials: A
authors.lastname: Costa
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D015152:Blotting, Northern; D015139:Blotting, Southern; D006528:Carcinoma, Hepatocellular / Q000201:enzymology*; D018450:Disease Progression; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology*; D008297:Male; D008780:Methyltransferases / Q000032:analysis* / Q000235:genetics; D008875:Middle Aged; D050918:Phosphatidylethanolamine N-Methyltransferase; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D008780:Methyltransferases; C494489:PEMT protein, human; D050918:Phosphatidylethanolamine N-Methyltransferase