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| Status |
Public on Jan 01, 2018 |
| Title |
Expression profiles of Brg1-depleted acinar cells during ductal conversion |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Brahma related gene 1 (BRG1), a catalytic ATPase subunit of SWI/SNF chromatin remodeling complexes, is silenced in approximately 10% of human pancreatic ductal adenocarcinomas (PDA). We previously showed that BRG1 inhibits the formation of intraductal pancreatic mucinous neoplasm (IPMN) and IPMN-derived PDA from ductal cells. However, the role of BRG1 in pancreatic intraepithelial neoplasia (PanIN) from acinar cells remains elusive. Here, we investigated the role of BRG1 in PanIN initiation and maintenance and its underlying mechanisms. Exclusive elimination of Brg1 in acinar cells of Ptf1a-CreER; KrasG12D; Brg1f/f (KBC) mice impaired the formation of acinar-to-ductal metaplasia (ADM) and PanIN independent of the presence of p53 mutation. We found that Sox9 expression was down-regulated in both Brg1-depleted acinar cell explants and BRG1-depleted ADMs/PanINs. Sox9 overexpression rescued this PanIN-attenuated phenotype in KBC mice. Furthermore, Brg1-deletion in established PanIN by using an inducible dual recombinase system resulted in regression of the lesions in mice. Finally, expression of BRG1 and SOX9 was also positively correlated in human PanIN-derived PDAs. In summary, BRG1 is critical for both initiation and maintenance of PanIN. Mechanistically, this is mediated through positive regulation of SOX9 expression. Thus, the BRG1/SOX9 axis is a potential target for the prevention of PanIN-derived PDA.
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| Overall design |
Total pooled RNA from three individual acinar cell explants 24 h after Cre-expressing adenovirus infection were used. Mouse genotypes used for analysis were KrasG12D and KrasG12D; Brg1f/f.
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| Contributor(s) |
Tsuda M, Fukuda A |
| Citation(s) |
30010625 |
| |
| Submission date |
Jan 13, 2017 |
| Last update date |
Jun 13, 2020 |
| Contact name |
Motoyuki Tsuda |
| E-mail(s) |
mtsuda@kuhp.kyoto-u.ac.jp
|
| Phone |
81(75)7514319
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| Organization name |
Graduate School of Medicine, Kyoto university
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| Department |
Department of Gastroenterology and Hepatology
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| Street address |
54 Kawahara-cho, Shogoin, Sakyo-ku
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| City |
kyoto |
| State/province |
Please Select |
| ZIP/Postal code |
606-8507 |
| Country |
Japan |
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| Platforms (1) |
| GPL21163 |
Agilent-074809 SurePrint G3 Mouse GE v2 8x60K Microarray [Probe Name version] |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA361287 |
