Format

Send to

Choose Destination
See comment in PubMed Commons below
PLoS One. 2014 May 1;9(5):e95486. doi: 10.1371/journal.pone.0095486. eCollection 2014.

Dicer regulates differentiation and viability during mouse pancreatic cancer initiation.

Author information

1
Diabetes Center, Department of Medicine, University of California San Francisco, San Francisco, California, United States of America.
2
Department of Pathology, University of California San Francisco, San Francisco, California, United States of America.
3
Department of Microbiology and Molecular Genetics, University of California Irvine, Irvine, California, United States of America.
4
Department of Developmental Biology, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California, United States of America.

Abstract

miRNA levels are altered in pancreatic ductal adenocarcinoma (PDA), the most common and lethal pancreatic malignancy, and intact miRNA processing is essential for lineage specification during pancreatic development. However, the role of miRNA processing in PDA has not been explored. Here we study the role of miRNA biogenesis in PDA development by deleting the miRNA processing enzyme Dicer in a PDA mouse model driven by oncogenic Kras. We find that loss of Dicer accelerates Kras driven acinar dedifferentiation and acinar to ductal metaplasia (ADM), a process that has been shown to precede and promote the specification of PDA precursors. However, unconstrained ADM also displays high levels of apoptosis. Dicer loss does not accelerate development of Kras driven PDA precursors or PDA, but surprisingly, we observe that mouse PDA can develop without Dicer, although at the expense of proliferative capacity. Our data suggest that intact miRNA processing is involved in both constraining pro-tumorigenic changes in pancreatic differentiation as well as maintaining viability during PDA initiation.

PMID:
24788257
PMCID:
PMC4006805
DOI:
10.1371/journal.pone.0095486
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Public Library of Science Icon for PubMed Central
    Loading ...
    Support Center