Dicer Regulates Differentiation and Viability during Mouse Pancreatic Cancer Initiation

被引：24

作者：

Morris, John P. ^{[1
]}

Greer, Renee ^{[1
]}

Russ, Holger A. ^{[1
]}

von Figura, Guido ^{[1
]}

Kim, Grace E. ^{[2
]}

Busch, Anke ^{[3
]}

Lee, Jonghyeob ^{[4
]}

Hertel, Klemens J. ^{[3
]}

Kim, Seung ^{[4
]}

Mcmanus, Michael ^{[1
]}

Hebrok, Matthias ^{[1
]}

机构：

[1] Univ Calif San Francisco, Dept Med, Ctr Diabet, San Francisco, CA 94117 USA

[2] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94140 USA

[3] Univ Calif San Francisco, Dept Microbiol & Mol Genet, San Francisco, CA 94143 USA

[4] Stanford Univ, Howard Hughes Med Inst, Sch Med, Dept Dev Biol, Stanford, CA 94305 USA

来源：

PLOS ONE | 2014年 / 9卷 / 05期

关键词：

MICRORNA EXPRESSION; ONCOGENIC KRAS; INTRAEPITHELIAL NEOPLASIA; DUCTAL ADENOCARCINOMA; PROGENITOR CELLS; GENE-EXPRESSION; ADULT MICE; TUMORIGENESIS; PROGRESSION; PATHWAY;

D O I：

10.1371/journal.pone.0095486

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：11

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