@article{fdd1ee69ed014c218a64e6ff83998a54,
title = "Context-Dependent Transformation of Adult Pancreatic Cells by Oncogenic K-Ras",
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.",
keywords = "CELLCYCLE",
author = "Friedlander, {Sharon Y.Gidekel} and Chu, {Gerald C.} and Snyder, {Eric L.} and Nomeda Girnius and Gregory Dibelius and Denise Crowley and Eliza Vasile and DePinho, {Ronald A.} and Tyler Jacks",
note = "Funding Information: We are grateful to D. Melton for gifts of the Pdx1CreER TM , proCPA1CreER T2 , and RipCreER TM strains and stimulating discussions. We thank A. Berns (Netherlands Cancer Institute) for providing the Trp53 flox mice; C. Wright for the anti-Pdx1 antibody; S. Hoersch for statistical analysis; and N. Bardeesy for critical reading of the manuscript. T.J. is a Howard Hughes Medical Institute Investigator and a Daniel K. Ludwig Scholar. S.Y.G.F. is an Anna Fuller fund of New Haven Fellow. R.A.D. is an American Cancer Society Research Professor. This work was supported by grant 1-PO1-CA117969-01 from the National Institutes of Health (NIH) and in part by Cancer Center Support (core) grant P30-CA14051 from the National Cancer Institute (NCI). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NCI or the NIH. ",
year = "2009",
month = nov,
day = "6",
doi = "10.1016/j.ccr.2009.09.027",
language = "English (US)",
volume = "16",
pages = "379--389",
journal = "Cancer cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "5",
}