Breast Cancer Research and Treatment

, Volume 135, Issue 1, pp 79–91

Whole genome in vivo RNAi screening identifies the leukemia inhibitory factor receptor as a novel breast tumor suppressor

Authors

    • Department of Medicine, School of MedicineUniversity of Miami
  • Toby M. Ward
    • Department of Medicine, School of MedicineUniversity of Miami
  • Sonja Dean
    • Department of Medicine, School of MedicineUniversity of Miami
  • Anna Jegg
    • Department of Medicine, School of MedicineUniversity of Miami
  • Dafydd Thomas
    • Department of PathologyUniversity of Michigan Cancer Center
  • Nirupa Murugaesu
    • The Breakthrough Breast Cancer Research CentreThe Institute of Cancer Research
  • David Sims
    • The Breakthrough Breast Cancer Research CentreThe Institute of Cancer Research
  • Costas Mitsopoulos
    • The Breakthrough Breast Cancer Research CentreThe Institute of Cancer Research
  • Kerry Fenwick
    • The Breakthrough Breast Cancer Research CentreThe Institute of Cancer Research
  • Iwanka Kozarewa
    • The Breakthrough Breast Cancer Research CentreThe Institute of Cancer Research
  • Cristina Naceur-Lombarelli
    • The Breakthrough Breast Cancer Research CentreThe Institute of Cancer Research
  • Marketa Zvelebil
    • The Breakthrough Breast Cancer Research CentreThe Institute of Cancer Research
  • Clare M. Isacke
    • The Breakthrough Breast Cancer Research CentreThe Institute of Cancer Research
  • Christopher J. Lord
    • The Breakthrough Breast Cancer Research CentreThe Institute of Cancer Research
  • Alan Ashworth
    • The Breakthrough Breast Cancer Research CentreThe Institute of Cancer Research
  • H. James Hnatyszyn
    • Department of Medicine, School of MedicineUniversity of Miami
  • Mark Pegram
    • Department of Medicine, School of MedicineUniversity of Miami
  • Marc Lippman
    • Department of Medicine, School of MedicineUniversity of Miami
Preclinical study

DOI: 10.1007/s10549-012-2068-7

Cite this article as:
Iorns, E., Ward, T.M., Dean, S. et al. Breast Cancer Res Treat (2012) 135: 79. doi:10.1007/s10549-012-2068-7

Abstract

Cancer is caused by mutations in oncogenes and tumor suppressor genes, resulting in the deregulation of processes fundamental to the normal behavior of cells. The identification and characterization of oncogenes and tumor suppressors has led to new treatment strategies that have significantly improved cancer outcome. The advent of next generation sequencing has allowed the elucidation of the fine structure of cancer genomes, however, the identification of pathogenic changes is complicated by the inherent genomic instability of cancer cells. Therefore, functional approaches for the identification of novel genes involved in the initiation and development of tumors are critical. Here we report the first whole human genome in vivo RNA interference screen to identify functionally important tumor suppressor genes. Using our novel approach, we identify previously validated tumor suppressor genes including TP53 and MNT, as well as several novel candidate tumor suppressor genes including leukemia inhibitory factor receptor (LIFR). We show that LIFR is a key novel tumor suppressor, whose deregulation may drive the transformation of a significant proportion of human breast cancers. These results demonstrate the power of genome wide in vivo RNAi screens as a method for identifying novel genes regulating tumorigenesis.

Keywords

Leukemia inhibitory factor receptorTumor suppressor geneIn vivo RNA interference screenBreast cancer

Supplementary material

10549_2012_2068_MOESM1_ESM.doc (154 kb)
Supplementary material 1 (DOC 154 kb)
10549_2012_2068_MOESM2_ESM.tif (2.9 mb)
Supplementary material 2 (TIFF 2931 kb)
10549_2012_2068_MOESM3_ESM.tif (2.9 mb)
Supplementary material 3 (TIFF 2931 kb)
10549_2012_2068_MOESM4_ESM.tif (2.9 mb)
Supplementary material 4 (TIFF 2931 kb)

Copyright information

© Springer Science+Business Media, LLC. 2012