Transgenic overexpression of a dominant negative mutant of FADD that, although counterselected during tumor progression, cooperates in L-myc-induced tumorigenesis

International Journal of Cancer. Journal International Du Cancer
Anne-Odile HueberMartin Zörnig

Abstract

Activation of the so-called death receptors, e.g., CD95/Fas/Apo-1, is a potent stimulus to trigger apoptosis. Overexpression of the C-terminal FADD deletion mutant FADD-DN blocks death receptor-induced apoptosis, but despite this antiapoptotic activity, lck FADD-DN transgenic mice do not develop lymphomas. To analyze whether functional inactivation of FADD cooperates with Myc overexpression in tumorigenesis, lck FADD-DN transgenic mice were crossed with Emicro L-myc transoncogenic animals. While no tumors were detected in single transgenic FADD-DN or L-myc mice within 15 months, 5 of 17 (29%) FADD-DN/L-myc double transgenic animals developed lymphomas with an average latency period of 47 weeks. Protein analysis of FADD-DN/L-myc tumors showed, however, undetectable levels of FADD-DN protein. FADD-DN protein expression was again lost in 16 of 17 FADD-DN/p53 k.o. T-cell lymphomas, though no significant acceleration of tumorigenesis in P53-deficient lck FADD-DN mice compared to p53 k.o. animals was observed. These data suggest a strong counterselection against the FADD-DN protein during tumor progression, which could be explained by the cell cycle inhibitory activity of FADD-DN. Such counterselection would have to be compensated fo...Continue Reading

References

Nov 17, 1995·The Journal of Biological Chemistry·R C Muise-Helmericks, N Rosen
May 31, 1996·The Journal of Biological Chemistry·C Borner
Sep 3, 1996·Proceedings of the National Academy of Sciences of the United States of America·G P LinetteS J Korsmeyer
May 20, 1998·Current Biology : CB·S A MarstersA Ashkenazi
May 20, 1998·Immunity·C M WalshS M Hedrick
Oct 14, 1998·Trends in Genetics : TIG·A O Hueber, G I Evan
Jan 27, 2000·Cell·D Hanahan, R A Weinberg
Apr 27, 2000·Nature Cell Biology·J L BodmerJ Tschopp
Mar 30, 2001·The Journal of Biological Chemistry·A YamadaK Takatsu
Aug 21, 2001·The Journal of Investigative Dermatology·R R BullaniL E French
Oct 10, 2001·Biochimica Et Biophysica Acta·M ZörnigG Evan
May 22, 2002·Journal of Hepato-biliary-pancreatic Surgery·Paula GhanehJohn P Neoptolemos
May 25, 2002·Cancer Investigation·Glenda GobéRalph Buttyan
Dec 4, 2002·Journal of Cellular Biochemistry·Katerina V Gurova, Andrei V Gudkov
Dec 18, 2002·Cytokine & Growth Factor Reviews·Harald WajantPeter Scheurich
Mar 26, 2003·Seminars in Cancer Biology·Irina V LebedevaPaul B Fisher
Mar 26, 2003·Cell Death and Differentiation·Lars E French, Jürg Tschopp
May 29, 2003·Current Medicinal Chemistry. Anti-cancer Agents·Simone Fulda, Klaus-Michael Debatin
Sep 5, 2003·The Journal of Biological Chemistry·Elizabeth C AlappatMarcus E Peter
Oct 14, 2003·Biochemical Pharmacology·Upasna Gaur, Bharat B Aggarwal
Nov 7, 2003·Journal of Clinical Immunology·Anjana Bhardwaj, Bharat B Aggarwal
Nov 25, 2003·Oncogene·Suzanne CoryJerry M Adams
Dec 4, 2003·Current Opinion in Cell Biology·Kelly M Boatright, Guy S Salvesen
Dec 10, 2003·Oncogene·Jonas A Nilsson, John L Cleveland
Mar 5, 2004·Biochimica Et Biophysica Acta·Vladimir KirkinMartin Zörnig

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Citations

Sep 10, 2011·Experimental Cell Research·Kristiina JärvinenErkki Hölttä

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