Bric, A., Miething, C., Bialucha, C. U., Scuoppo, C., Zender, L., Krasnitz, A., Xuan, Z., Zuber, J., Wigler, M. H., Hicks, J. B., McCombie, W. R., Hemann, M. T., Hannon, G. J., Powers, S., Lowe, S. W.
(October 2009)
Functional identification of tumor-suppressor genes through an in vivo RNA interference screen in a mouse lymphoma model.
Cancer Cell, 16 (4).
pp. 324-35.
ISSN 1535-6108
Abstract
Short hairpin RNAs (shRNAs) capable of stably suppressing gene function by RNA interference (RNAi) can mimic tumor-suppressor-gene loss in mice. By selecting for shRNAs capable of accelerating lymphomagenesis in a well-characterized mouse lymphoma model, we identified over ten candidate tumor suppressors, including Sfrp1, Numb, Mek1, and Angiopoietin 2. Several components of the DNA damage response machinery were also identified, including Rad17, which acts as a haploinsufficient tumor suppressor that responds to oncogenic stress and whose loss is associated with poor prognosis in human patients. Our results emphasize the utility of in vivo RNAi screens, identify and validate a diverse set of tumor suppressors, and have therapeutic implications.
| Item Type: |
Paper
|
| Uncontrolled Keywords: |
Angiopoietin 2 genetics
Animals
Cell Cycle Proteins genetics
Cell Line Tumor
Cell Transformation Neoplastic genetics metabolism pathology
DNA Damage
Gene Expression Regulation Neoplastic
Genes Tumor Suppressor
Genes myc
Genes p53
Genetic Screening methods
Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cells metabolism
Humans
Intercellular Signaling Peptides and Proteins genetics
Lymphoma genetics metabolism pathology
MAP Kinase Kinase 1 genetics
Map
Membrane Proteins genetics
Mice
Mice Inbred C57BL
Nerve Tissue Proteins genetics
Prognosis
RNA Interference
RNAi
Reproducibility of Results
Time Factors
Transduction Genetic |
| Subjects: |
diseases & disorders > cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > RNAi
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > shRNA |
| CSHL Authors: |
Bialucha, Carl Uli
Bric, Anka
Hannon, Gregory J.
Hicks, James B.
Krasnitz, Alexander
Lowe, Scott W.
McCombie, W. Richard
Miething, Cornelius
Powers, Scott
Scuoppo, Claudio
Wigler, Michael H.
Xuan, Zhenyu Y.
Zender, Lars
Zuber, Johannes
|
| Communities: |
CSHL labs > Hannon lab
CSHL labs > Hicks lab
CSHL labs > Krasnitz lab
CSHL labs > Lowe lab
CSHL labs > McCombie lab
CSHL labs > Powers lab
CSHL labs > Wigler lab
CSHL Cancer Center Shared Resources > Animal Services
CSHL Cancer Center Shared Resources > Antibody and Phage Display Service
CSHL Cancer Center Shared Resources > Bioinformatics Service
School of Biological Sciences > Publications
CSHL Cancer Center Shared Resources > DNA Sequencing Service
CSHL Cancer Center Shared Resources > Flow Cytometry Service
CSHL Cancer Center Shared Resources > Gene Targeting Service
CSHL Cancer Center Shared Resources > Instrumentation Service
CSHL Cancer Center Shared Resources > Microscopy Service |
| Depositing User: |
Editor Margaret Fantz
|
| Date: |
6 October 2009 |
| Date Deposited: |
08 May 2012 17:46 |
| Last Modified: |
30 Dec 2014 16:04 |
| PMCID: |
PMC2829755 |
| Related URLs: |
|
| URI: |
https://repository.cshl.edu/id/eprint/26052 |
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