Successful growth and characterization of mouse pancreatic ductal cells: functional properties of the Ki-RAS(G12V) oncogene

Gastroenterology
Franz S SchreiberAnil K Rustgi

Abstract

The Ki-RAS oncogene is altered in pancreatic ductal neoplasms. Pancreatic ductal cells (PDCs) were purified from cytokeratin 19 (K19)-Ki-RAS(G12V) transgenic mice and control littermates to identify properties of Ki-Ras activation in a cell-type-specific context. Because Ki-RAS mutation has prognostic significance in patients treated with radiation, we studied the influence of Ki-RAS status on radiation survival. Pancreatic ductal fragments from mice with Ki-RAS(G12V) mutation or wild-type (WT)-Ki-RAS were cultured. Growth curves, electron microscopy, flow cytometry, and analysis of signaling and cell-cycle proteins were established. Farnesyltransferase inhibitor (FTI) treatment with R115777 before and after irradiation was used to determine the effect of Ki-Ras farnesylation on cell survival. PDCs from WT and K19-Ki-RAS(G12V) mice had features of ductal cells with formation of 3-dimensional structures on collagen without differences in morphology, growth, and cell-cycle distribution. This may result from up-regulation of p16INK4 and p27(Kip1) and lack of hyperstimulation of the mitogen-activated protein kinase pathway in Ki-RAS(G12V) PDCs. No differences in radiation survival between Ki-RAS(G12V) PDCs and WT PDCs were observed...Continue Reading

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Citations

Nov 26, 2009·Nature Cell Biology·Ulrich WellnerThomas Brabletz
Jun 22, 2013·Nature Protocols·Maximilian ReichertAnil K Rustgi
Feb 23, 2013·Proceedings of the National Academy of Sciences of the United States of America·Liang JinHsun Teresa Ku
Feb 22, 2012·The Journal of Experimental Medicine·Natalie CookDavid A Tuveson
Oct 2, 2009·Molecular Biology of the Cell·Melanie P WescottAnil K Rustgi
Dec 3, 2011·The Journal of Clinical Investigation·Maximilian Reichert, Anil K Rustgi
Apr 18, 2008·PLoS Medicine·Kimberly A KellyRalph Weissleder
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Oct 24, 2006·The Journal of Biological Chemistry·Therese B DeramaudtAnil K Rustgi

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