title: High expression of methionine aminopeptidase 2 in human colorectal adenocarcinomas.
abstract: OBJECTIVE
  Several viral and eukaryotic proteins required for signal transduction and regulatory functions undergo lipophilic modification by the enzyme N-myristoyltransferase. Previously we reported that N-myristoyltransferase activity is higher in colon and gallbladder carcinoma than in the corresponding normal tissues. Methionine aminopeptidase 2 (MetAP2) is a bifunctional protein that plays a critical role in the regulation of post-translational processing and protein synthesis. To investigate whether MetAP2 contributes to the pathogenesis of colon carcinoma, we investigated the expression of MetAP2 in both normal and invasive tumor components of human samples.
  
  
  METHODS
  We evaluated 50 cases of colon carcinoma for this study. In this report we analyzed 15 cases for MetAP2 activity and 13 cases for the expression of MetAP2 by Western blot in both the normal and in invasive tumor components of human samples. In addition, immunohistochemistry analysis was also carried out on samples from all patients.
  
  
  RESULTS
  MetAP activity was elevated in all cancerous tissues compared with normal tissues. Western blot analysis also showed the higher expression of MetAP2 in all cases of cancerous tissues. In addition, immunohistochemistry analysis revealed that all cases of colorectal adenocarcinoma showed moderate to strong cytoplasmic positivity for MetAP2 with increased intensity in the invasive component.
  
  
  CONCLUSIONS
  Elevated MetAP protein expression is associated with metastatic tumor progression and appears to be a strong molecular marker for clinical prognosis. MetAP2 inhibition may represent a potential target for therapeutic intervention in colorectal carcinoma.
authors.affiliation: Department of Pathology, College of Medicine and Health Research Division, Saskatchewan Cancer Agency, Saskatoon, Canada.
authors.forename: Ponniah
authors.initials: P
authors.lastname: Selvakumar
authors.forename: Ashakumary
authors.initials: A
authors.lastname: Lakshmikuttyamma
authors.forename: Rani
authors.initials: R
authors.lastname: Kanthan
authors.forename: Selliah Chandra
authors.initials: SC
authors.lastname: Kanthan
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Dimmock
authors.forename: Rajendra K
authors.initials: RK
authors.lastname: Sharma
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology*; D000626:Aminopeptidases / Q000096:biosynthesis*; D015153:Blotting, Western; D003106:Colon / Q000473:pathology; D015179:Colorectal Neoplasms / Q000201:enzymology*; D003593:Cytoplasm / Q000378:metabolism; D018450:Disease Progression; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007150:Immunohistochemistry; D008666:Metalloendopeptidases / Q000096:biosynthesis*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011379:Prognosis; D011499:Protein Processing, Post-Translational; D012007:Rectum / Q000473:pathology
chemical_list: D000626:Aminopeptidases; C106541:methionine aminopeptidase 2; D008666:Metalloendopeptidases