PMID- 17450475
OWN - NLM
STAT- MEDLINE
DCOM- 20071002
LR  - 20151119
IS  - 0284-186X (Print)
IS  - 0284-186X (Linking)
VI  - 46
IP  - 3
DP  - 2007
TI  - Methionine aminopeptidase 2 over-expressed in cholangiocarcinoma: potential for 
      drug target.
PG  - 378-85
AB  - Methionine aminopeptidases (MetAP) are proteases which remove the N-terminal 
      methionine from newly synthesized proteins. Associations of MetAP2 with tumor 
      progression of different cancers have been repeatedly reported. We aim to 
      determine if MetAP2 is expressed in cholangiocarcinomas (CCA) and investigate to 
      see if it would be a useful therapeutic target. We evaluated MetAP2 expression by 
      immunohistochemistry in 82 patients of intrahepatic CCA. MetAP2 was expressed in 
      bile ducts to various degrees. It was occasionally expressed with weak staining 
      in normal bile duct epithelium but was strikingly over-expressed in dysplastic 
      bile duct epithelia, primary and metastatic CCA tissues (p < 0.001). The 
      increased expression of MetAP2 in proliferating bile duct was evident. All 
      metastatic tumors had stronger expression of MetAP2 than the corresponding 
      primary tumors. Fumagillin, a MetAP2 specific inhibitor, significantly inhibited 
      cell proliferation in dose dependent manner and the degree of growth inhibition 
      was dependent on the amount of cellular enzyme. The present study highlights the 
      involvement of MetAP2 in an early event of carcinogenesis of CCA. The findings 
      represent the first description of increased MetAP2 expression in CCA. The 
      inhibition of enzyme activity using MetAP2 inhibitors may be a potential strategy 
      for long-term control of tumor development and progression in CCA patients.
FAU - Sawanyawisuth, Kanlayanee
AU  - Sawanyawisuth K
AD  - Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 
      40002, Thailand.
FAU - Wongkham, Chaisiri
AU  - Wongkham C
FAU - Pairojkul, Chawalit
AU  - Pairojkul C
FAU - Saeseow, O-Tur
AU  - Saeseow OT
FAU - Riggins, Gregory J
AU  - Riggins GJ
FAU - Araki, Norie
AU  - Araki N
FAU - Wongkham, Sopit
AU  - Wongkham S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Sweden
TA  - Acta Oncol
JT  - Acta oncologica (Stockholm, Sweden)
JID - 8709065
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Cyclohexanes)
RN  - 0 (Fatty Acids, Unsaturated)
RN  - 0 (Sesquiterpenes)
RN  - 7OW73204U1 (fumagillin)
RN  - EC 3.4.11.- (Aminopeptidases)
RN  - EC 3.4.11.18 (methionine aminopeptidase 2)
RN  - EC 3.4.24.- (Metalloendopeptidases)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aminopeptidases/*biosynthesis/*drug effects
MH  - Angiogenesis Inhibitors/pharmacology
MH  - Bile Duct Neoplasms/drug therapy/*metabolism/pathology
MH  - Bile Ducts, Intrahepatic/cytology/drug effects/*enzymology/*pathology
MH  - Biomarkers, Tumor/blood
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Cholangiocarcinoma/drug therapy/*metabolism/pathology
MH  - Cyclohexanes/pharmacology
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Epithelium/drug effects/enzymology/pathology
MH  - Fatty Acids, Unsaturated/pharmacology
MH  - Female
MH  - Humans
MH  - Immunoblotting
MH  - Immunohistochemistry
MH  - Male
MH  - Metalloendopeptidases/*biosynthesis/*drug effects
MH  - Middle Aged
MH  - Neoplasm Invasiveness
MH  - Sesquiterpenes/pharmacology
MH  - Up-Regulation/drug effects
EDAT- 2007/04/24 09:00
MHDA- 2007/10/03 09:00
CRDT- 2007/04/24 09:00
PHST- 2007/04/24 09:00 [pubmed]
PHST- 2007/10/03 09:00 [medline]
PHST- 2007/04/24 09:00 [entrez]
AID - 777305653 [pii]
AID - 10.1080/02841860600871061 [doi]
PST - ppublish
SO  - Acta Oncol. 2007;46(3):378-85. doi: 10.1080/02841860600871061.