PMID- 19352382
OWN - NLM
STAT- MEDLINE
DCOM- 20090514
LR  - 20211020
IS  - 1532-1827 (Electronic)
IS  - 0007-0920 (Print)
IS  - 0007-0920 (Linking)
VI  - 100
IP  - 9
DP  - 2009 May 5
TI  - Hypermethylation-mediated reduction of WWOX expression in intraductal papillary 
      mucinous neoplasms of the pancreas.
PG  - 1438-43
LID - 10.1038/sj.bjc.6604986 [doi]
AB  - We have previously shown that WW domain-containing oxidoreductase (WWOX) has 
      tumour-suppressing effects and that its expression is frequently reduced in 
      pancreatic carcinoma. In this study, we examined WWOX expression in intraductal 
      papillary mucinous neoplasm of the pancreas (IPMN) to assess the function of WWOX 
      in pancreatic duct tumourigenesis using immunohistochemistry and 
      methylation-specific polymerase chain reaction analysis. Among 41 IPMNs including 
      intraductal papillary mucinous adenomas (IPMAs) and intraductal papillary 
      mucinous carcinomas (IPMCs), loss or reduced WWOX immunoreactivity was detected 
      in 3 (15%) of 20 IPMAs and 17 (81%) of 21 IPMCs. In addition, hypermethylation of 
      the WWOX regulatory site was detected in 1 (33%) of 3 WWOX(-) IPMAs and 9 (53%) 
      of 17 WWOX(-) IPMCs, suggesting that hypermethylation may possibly be important 
      in the suppression of WWOX expression. Reduction of WWOX expression was 
      significantly correlated with a higher Ki-67 labelling index but was not 
      correlated with the ssDNA apoptotic body index. Interestingly, decreased WWOX 
      expression was significantly correlated with loss of SMAD4 expression in these 
      IPMNs. The results indicate that downregulation of WWOX expression by the WWOX 
      regulatory region hypermethylation is critical for transformation of pancreatic 
      duct.
FAU - Nakayama, S
AU  - Nakayama S
AD  - Division of Pathology, Department of Pathology, Kobe University Graduate School 
      of Medicine, Kobe, Japa.
FAU - Semba, S
AU  - Semba S
FAU - Maeda, N
AU  - Maeda N
FAU - Matsushita, M
AU  - Matsushita M
FAU - Kuroda, Y
AU  - Kuroda Y
FAU - Yokozaki, H
AU  - Yokozaki H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090407
PL  - England
TA  - Br J Cancer
JT  - British journal of cancer
JID - 0370635
RN  - 0 (DNA, Neoplasm)
RN  - 0 (DNA, Single-Stranded)
RN  - 0 (Tumor Suppressor Proteins)
RN  - EC 1.- (Oxidoreductases)
RN  - EC 1.1.1.- (WW Domain-Containing Oxidoreductase)
RN  - EC 1.1.1.- (WWOX protein, human)
SB  - IM
MH  - Adenocarcinoma, Mucinous/*genetics/pathology
MH  - Aged
MH  - Carcinoma, Papillary/*genetics/pathology
MH  - Cell Line, Tumor
MH  - DNA Methylation/*genetics
MH  - DNA, Neoplasm/genetics
MH  - DNA, Single-Stranded/genetics
MH  - Down-Regulation
MH  - Female
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Immunohistochemistry
MH  - Male
MH  - Oxidoreductases/*deficiency/*genetics
MH  - Pancreatic Neoplasms/*genetics/pathology
MH  - Polymerase Chain Reaction
MH  - *Suppression, Genetic
MH  - Tumor Suppressor Proteins/*deficiency/*genetics
MH  - WW Domain-Containing Oxidoreductase
PMC - PMC2694421
EDAT- 2009/04/09 09:00
MHDA- 2009/05/15 09:00
PMCR- 2010/05/05
CRDT- 2009/04/09 09:00
PHST- 2009/04/09 09:00 [entrez]
PHST- 2009/04/09 09:00 [pubmed]
PHST- 2009/05/15 09:00 [medline]
PHST- 2010/05/05 00:00 [pmc-release]
AID - 6604986 [pii]
AID - 10.1038/sj.bjc.6604986 [doi]
PST - ppublish
SO  - Br J Cancer. 2009 May 5;100(9):1438-43. doi: 10.1038/sj.bjc.6604986. Epub 2009 
      Apr 7.