Format

Send to

Choose Destination
Cancer Cell. 2012 Dec 11;22(6):737-50. doi: 10.1016/j.ccr.2012.10.025. Epub 2012 Nov 29.

Identification of Sox9-dependent acinar-to-ductal reprogramming as the principal mechanism for initiation of pancreatic ductal adenocarcinoma.

Author information

1
Departments of Pediatrics and Cellular and Molecular Medicine, University of California-San Diego, La Jolla, CA 92093-0695, USA.

Abstract

Tumors are largely classified by histologic appearance, yet morphologic features do not necessarily predict cellular origin. To determine the origin of pancreatic ductal adenocarcinoma (PDA), we labeled and traced pancreatic cell populations after induction of a PDA-initiating Kras mutation. Our studies reveal that ductal and stem-like centroacinar cells are surprisingly refractory to oncogenic transformation, whereas acinar cells readily form PDA precursor lesions with ductal features. We show that formation of acinar-derived premalignant lesions depends on ectopic induction of the ductal gene Sox9. Moreover, when concomitantly expressed with oncogenic Kras, Sox9 accelerates formation of premalignant lesions. These results provide insight into the cellular origin of PDA and suggest that its precursors arise via induction of a duct-like state in acinar cells.

PMID:
23201164
PMCID:
PMC3568632
DOI:
10.1016/j.ccr.2012.10.025
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center