Modeling oncogene addiction using RNA interference
作者： S. M. Rothenberg , J. A. Engelman , S. Le , D. J. Riese , D. A. Haber
关键词:
摘要: The clinical efficacy of selective kinase inhibitors suggests that some cancer cells may become dependent on a single oncogene for survival. RNAi has been increasingly used to understand such "oncogene addiction" and validate new therapeutic targets. However, approaches suffer from significant off-target effects limit their utility. Here, we combine carefully titrated lentiviral-mediated short hairpin RNA knockdown the epidermal growth factor receptor (EGFR) with heterologous reconstitution by EGFR mutants rigorously analyze structural features signaling activities determine addiction mutationally activated in human lung cells. dependence is differentially rescued distinct variants oncogenic mutants, critically its heterodimerization partner ErbB-3, surprisingly, does not require autophosphorylation sites cytoplasmic domain. Quantitative rescue" analysis allows mechanistic dissection addiction, and, when broadly applied, provide functional validation potential targets identified through large-scale screens.
harvard.edu
jstor.org 
sci-hub.se 参考文章(28)
Lynda Chin, Alice Tam, Jason Pomerantz, Michelle Wong, Jocelyn Holash, Nabeel Bardeesy, Qiong Shen, Ronan O'Hagan, Joe Pantginis, Hao Zhou, James W. Horner, Carlos Cordon-Cardo, George D. Yancopoulos, Ronald A. DePinho#, Essential role for oncogenic Ras in tumour maintenance Nature. ,vol. 400, pp. 468- 472 ,(1999) , 10.1038/22788
Claudia S. Huettner, Pu Zhang, Richard A. Van Etten, Daniel G. Tenen, Reversibility of acute B-cell leukaemia induced by BCR-ABL1. Nature Genetics. ,vol. 24, pp. 57- 60 ,(2000) , 10.1038/71691
Dirk Grimm, Konrad L. Streetz, Catherine L. Jopling, Theresa A. Storm, Kusum Pandey, Corrine R. Davis, Patricia Marion, Felix Salazar, Mark A. Kay, Fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways. Nature. ,vol. 441, pp. 537- 541 ,(2006) , 10.1038/NATURE04791
Alan J Bridge, Stephanie Pebernard, Annick Ducraux, Anne-Laure Nicoulaz, Richard Iggo, Induction of an interferon response by RNAi vectors in mammalian cells Nature Genetics. ,vol. 34, pp. 263- 264 ,(2003) , 10.1038/NG1173
William Pao, Vincent A Miller, Katerina A Politi, Gregory J Riely, Romel Somwar, Maureen F Zakowski, Mark G Kris, Harold Varmus, Acquired Resistance of Lung Adenocarcinomas to Gefitinib or Erlotinib Is Associated with a Second Mutation in the EGFR Kinase Domain PLoS Medicine. ,vol. 2, pp. e73- ,(2005) , 10.1371/JOURNAL.PMED.0020073
R. Nishikawa, X. D. Ji, R. C. Harmon, C. S. Lazar, G. N. Gill, W. K. Cavenee, H. J. Huang, A mutant epidermal growth factor receptor common in human glioma confers enhanced tumorigenicity. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 91, pp. 7727- 7731 ,(1994) , 10.1073/PNAS.91.16.7727
Dean W. Felsher, J.Michael Bishop, Reversible Tumorigenesis by MYC in Hematopoietic Lineages Molecular Cell. ,vol. 4, pp. 199- 207 ,(1999) , 10.1016/S1097-2765(00)80367-6
Aimee L Jackson, Steven R Bartz, Janell Schelter, Sumire V Kobayashi, Julja Burchard, Mao Mao, Bin Li, Guy Cavet, Peter S Linsley, Expression profiling reveals off-target gene regulation by RNAi Nature Biotechnology. ,vol. 21, pp. 635- 637 ,(2003) , 10.1038/NBT831
Christopher Greenman, Philip Stephens, Raffaella Smith, Gillian L. Dalgliesh, Christopher Hunter, Graham Bignell, Helen Davies, Jon Teague, Adam Butler, Claire Stevens, Sarah Edkins, Sarah O’Meara, Imre Vastrik, Esther E. Schmidt, Tim Avis, Syd Barthorpe, Gurpreet Bhamra, Gemma Buck, Bhudipa Choudhury, Jody Clements, Jennifer Cole, Ed Dicks, Simon Forbes, Kris Gray, Kelly Halliday, Rachel Harrison, Katy Hills, Jon Hinton, Andy Jenkinson, David Jones, Andy Menzies, Tatiana Mironenko, Janet Perry, Keiran Raine, Dave Richardson, Rebecca Shepherd, Alexandra Small, Calli Tofts, Jennifer Varian, Tony Webb, Sofie West, Sara Widaa, Andy Yates, Daniel P. Cahill, David N. Louis, Peter Goldstraw, Andrew G. Nicholson, Francis Brasseur, Leendert Looijenga, Barbara L. Weber, Yoke-Eng Chiew, Anna deFazio, Mel F. Greaves, Anthony R. Green, Peter Campbell, Ewan Birney, Douglas F. Easton, Georgia Chenevix-Trench, Min-Han Tan, Sok Kean Khoo, Bin Tean Teh, Siu Tsan Yuen, Suet Yi Leung, Richard Wooster, P. Andrew Futreal, Michael R. Stratton, Patterns of somatic mutation in human cancer genomes Nature. ,vol. 446, pp. 153- 158 ,(2007) , 10.1038/NATURE05610
Nadia Godin-Heymann, Ianthe Bryant, Miguel N. Rivera, Lindsey Ulkus, Daphne W. Bell, David J. Riese, Jeffrey Settleman, Daniel A. Haber, Oncogenic Activity of Epidermal Growth Factor Receptor Kinase Mutant Alleles Is Enhanced by the T790M Drug Resistance Mutation Cancer Research. ,vol. 67, pp. 7319- 7326 ,(2007) , 10.1158/0008-5472.CAN-06-4625