|
| Status |
Public on Nov 12, 2019 |
| Title |
Intraepithelial papillary neoplasia in the biliary tree is mediated by FGF10 signal |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
The new concept of neoplastic lesion of biliary tree, Biliary intraepithelial neoplasia (BilIN) and intraductal papillary neoplasm of bile duct (IPNB), as a conunterpart of pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasm (IPMN), have been reported to be precancerous lesions in hilar and extrahepatic cholangiocarcinoma and arise from lining bile duct epithelium and peribiliary gland (PBG) under inflammation microenvironment in human. However, mouse model is lacking different from intrahepatic cholangiocarcinoma arised from canal of Hering in the liver. In a Doxycyclin-controlled transgenic mouse model of BilIN and IPNB, overexpression of Fibroblast Growth Factor 10 (FGF10) phenocopies human pathology with mutistep progression of cholangiocarcinogenesis in chronic cholangitis. The development and branching morphogenesis of BilIN and IPNB was induced by Fgf10/Erk signal and inhibited by MEK inhibiter. Pdx1+ PBG cells present in IPNB were able to lineage trace the early IPNB lesion as well as Krt19+ cholangiocytes. BiliN and IPNB with Kras mutation was irreversible different from no Kras mutation, and loss of p16 contributed to malignant transformation of BilIN and IPNB. Our data challenge the common paradigms regarding the pathogenesis of BilIN and IPNB.
|
| |
|
| Overall design |
FGF10 overexpressed mice (n=3), no expressed control mice (n=3)
|
| |
|
| Contributor(s) |
Tomita H, Tanaka K, Hara A |
| Citation(s) |
33626352 |
| Submission date |
Aug 30, 2018 |
| Last update date |
Mar 03, 2021 |
| Contact name |
Hiroyuki Tomita |
| Organization name |
Gifu University
|
| Street address |
1-1 Yanagido
|
| City |
Gifu |
| ZIP/Postal code |
5011194 |
| Country |
Japan |
| |
|
| Platforms (1) |
| GPL21163 |
Agilent-074809 SurePrint G3 Mouse GE v2 8x60K Microarray [Probe Name version] |
|
| Samples (6)
|
|
| Relations |
| BioProject |
PRJNA488551 |
Less...
More...