Context-Dependent Transformation of Adult Pancreatic Cells by Oncogenic K-Ras
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Friedlander-2009-Context-Dependent Tr.pdf
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Author(s)
Friedlander, Sharon Y. Gidekel
Chu, Gerald C.
Snyder, Eric L.
Girnius, Nomeda
Dibelius, Gregory
Crowley, Denise G.
Vasile, Eliza
DePinho, Ronald A.
Jacks, Tyler E.
Date Issued
November 2009
Journal
Cancer Cell
Publisher
Elsevier B.V.
Citation
Friedlander, Sharon Y. Gidekel, Gerald C. Chu, Eric L. Snyder, Nomeda Girnius, Gregory Dibelius, Denise Crowley, Eliza Vasile, Ronald A. DePinho, and Tyler Jacks. “Context-Dependent Transformation of Adult Pancreatic Cells by Oncogenic K-Ras.” Cancer Cell 16, no. 5 (November 2009): 379–389. © 2009 Elsevier Inc.
Version
Final published version
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human malignancies. To investigate the cellular origin(s) of this cancer, we determined the effect of PDAC-relevant gene mutations in distinct cell types of the adult pancreas. We show that a subpopulation of Pdx1-expressing cells is susceptible to oncogenic K-Ras-induced transformation without tissue injury, whereas insulin-expressing endocrine cells are completely refractory to transformation under these conditions. However, chronic pancreatic injury can alter their endocrine fate and allow them to serve as the cell of origin for exocrine neoplasia. These results suggest that one mechanism by which inflammation and/or tissue damage can promote neoplasia is by altering the fate of differentiated cells that are normally refractory to oncogenic stimulation.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1016/j.ccr.2009.09.027
