Abstract
A broad range of malignant diseases, such as mantle cell lymphoma (MCL), is associated with complex genomic alterations, demanding multimodal functional testing of candidate genes. To assess such candidate disease genes, we have developed a bidirectional targeted transgenesis tool, which allows well-controlled modulation of individual gene activities within a cellular MCL system. The engineered versatile transgenesis system permits functional analysis of virtually any candidate gene: for tumor suppressor genes by complementation via integration of respective genomic DNA or for oncogenes by inactivation via integrated shRNA coding plasmids. Complementation by genomic DNA ensures wild-type (WT) regulated gene expression, whereas genomic integration of shRNA coding inserts by an advanced RNAi-strategy mediates specific knock-down of gene expression. Site-specific genomic integration of an unmodified BAC, which contains the CDKN2A/B genes absent in the MCL model system, restored CDKN2A/B expression resulting in the inhibition of cell proliferation. CCND1, strongly overexpressed in the model system, was down-regulated via shRNA expression, again inhibiting proliferation. Notably, the presented site-specific shRNA-strategy circumvent...Continue Reading
References
Nov 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·C L RosenbergA Arnold
Jun 6, 1995·Proceedings of the National Academy of Sciences of the United States of America·G RobertsonE Whitelaw
Jan 1, 1995·Methods in Enzymology·P LichterS Joos
Feb 1, 1996·Cancer Genetics and Cytogenetics·D GandiniL del Senno
Jan 1, 1997·Leukemia·D M JadayelD Catovsky
Dec 31, 1997·Genes, Chromosomes & Cancer·S Solinas-ToldoP Lichter
Feb 14, 1998·Nature Genetics·G SchiednerS Kochanek
Mar 5, 1998·Nature·A FireC C Mello
May 16, 1998·Oncogene·S StilgenbauerP Lichter
Jul 17, 1998·The American Journal of Pathology·L Quintanilla-MartinezM Raffeld
Dec 22, 1999·Leukemia·L HernándezE Campo
Dec 22, 1999·Annals of Hematology·P Meusers, J Hense
Mar 8, 2000·Proceedings of the National Academy of Sciences of the United States of America·C SchaffnerP Lichter
Mar 7, 2001·Genome Research·K OsoegawaP J de Jong
Oct 18, 2001·Current Opinion in Biotechnology·A Baer, J Bode
Jan 5, 2002·Molecular and Cellular Biology·Maria Kraakman-van der ZwetMalgorzata Z Zdzienicka
Feb 16, 2002·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·A BattistiniJ Hiscott
Mar 23, 2002·Science·Thijn R BrummelkampReuven Agami
May 31, 2002·Blood·Christian KorzPeter Lichter
Nov 1, 2002·Nucleic Acids Research·Matthias LauthMichael Meyer
Dec 11, 2002·The Journal of Pathology·Raymond LaiTimothy J McDonnell
Mar 7, 2003·Cancer Cell·Andreas RosenwaldLouis M Staudt
Apr 10, 2003·Archives of Pathology & Laboratory Medicine·Hesham M AminRaymond Lai
Jun 11, 2003·Nature Genetics·Alan J BridgeRichard Iggo
Aug 23, 2003·Oncogene·Hesham M AminRaymond Lai
Aug 28, 2003·Nature Cell Biology·Carol A SledzBryan R G Williams
Jun 19, 2004·Cancer Research·Mark D'AmicoRichard G Pestell
Feb 8, 2005·Proceedings of the National Academy of Sciences of the United States of America·Ralf KittlerFrank Buchholz
Apr 16, 2005·Nucleic Acids Research·Jost SeiblerFrieder Schwenk
Apr 19, 2006·Oncogene·L-C HsuS M Gollin
Citations
Dec 3, 2011·Acta Neuropathologica·Alfa H C BaiStefan M Pfister
Aug 22, 2013·Cancer Letters·Chonglin LuoStefan B Eichmüller
Jul 31, 2009·Leukemia·A FarfsingA Pscherer
Jan 2, 2013·Carcinogenesis·Qi WangJu-Xiang Chen
Jun 17, 2009·Nucleic Acids Research·Shuwen WangJiyue Zhu
Jul 29, 2010·Cancer Research·Rong ChenWilliam Plunkett
Nov 21, 2007·Blood·Eva Ortega-PainoCarl A K Borrebaeck
Jun 8, 2012·BMC Cancer·Evgeny A MoskalevJörg D Hoheisel
Aug 8, 2008·Leukemia·M KlierL Quintanilla-Martinez
Jan 19, 2011·Analytical Biochemistry·Christopher LössnerMartina Schnölzer
Dec 23, 2015·BMC Cancer·Chenran ZhangYicheng Lu
Aug 25, 2010·International Journal of Cancer. Journal International Du Cancer·Maria ShahmoradgoliPeter Lichter
Jun 5, 2015·Molecular Oncology·Pilar BayoJochen Hess
Nov 21, 2018·Head & Neck·Dominik HornKolja Freier
Aug 30, 2012·Nature Communications·Stephan DirenbergerOliver Griesbeck
Feb 3, 2012·Molekuliarnaia biologiia·E S KniazhanskaiaM B Gottikh
Sep 14, 2011·Journal of Neuro-oncology·Junyu WangYicheng Lu
Jun 6, 2009·Cancer Research·Stefanie HeckPeter Lichter
Oct 28, 2010·Cancer Research·Pedro de Souza Rocha SimoniniYasser Riazalhosseini