Gene expression profiling reveals upregulated UCA1 and BMF in gallbladder epithelia of children with pancreaticobiliary maljunction.
J Pediatr Gastroenterol Nutr
; 52(6): 744-50, 2011 Jun.
Article
in En
| MEDLINE
| ID: mdl-21593646
ABSTRACT
BACKGROUND:
Pancreaticobiliary maljunction is usually associated with choledochal cysts and often causes biliary carcinoma; however, the mechanism of carcinogenesis remains unknown. No study has analyzed overall changes in genetic expression beginning during childhood in gallbladder epithelia with pancreaticobiliary maljunction. PATIENTS ANDMETHODS:
The genomewide expression of gallbladder epithelia was analyzed in 6 children with pancreaticobiliary maljunction and in 4 pediatric controls. Selected genes that were expressed differentially were further analyzed by the real-time reverse transcription-polymerase chain reaction (RT-PCR). The products of upregulated genes confirmed by real-time RT-PCR were immunohistochemically analyzed using gallbladders from 19 children with pancreaticobiliary maljunction, 5 pediatric controls, and 5 children with gallstones.RESULTS:
Microarray analysis identified 188 upregulated and 160 downregulated genes. RT-PCR confirmed upregulation in 5 of 6 genes and downregulation in 1 of 5 genes, including UCA1, DUOX2, DUOXA2, ID1, BMF, and GP2. Immunohistochemistry showed a significantly higher expression of BMF in the pancreaticobiliary maljunction patients than in the controls and gallstone patients.CONCLUSIONS:
This study identified several deregulated genes in the gallbladder of children with pancreaticobiliary maljunction, which may contribute to the pathophysiology. UCA1, a noncoding RNA, is an oncofetal gene, and its upregulation may be important for biliary carcinogenesis. The elevated expression of BMF may function as an apoptotic activator in proliferative gallbladder epithelia.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pancreatic Diseases
/
Bile Duct Diseases
/
Gene Expression
/
RNA, Untranslated
/
Adaptor Proteins, Signal Transducing
/
Epithelium
/
Gallbladder
Limits:
Child
/
Child, preschool
/
Female
/
Humans
/
Male
Language:
En
Journal:
J Pediatr Gastroenterol Nutr
Year:
2011
Type:
Article
Affiliation country:
Japan