PMID- 19808965
OWN - NLM
STAT- MEDLINE
DCOM- 20091124
LR  - 20211020
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 69
IP  - 20
DP  - 2009 Oct 15
TI  - A modified sleeping beauty transposon system that can be used to model a wide 
      variety of human cancers in mice.
PG  - 8150-6
LID - 10.1158/0008-5472.CAN-09-1135 [doi]
AB  - Recent advances in cancer therapeutics stress the need for a better understanding 
      of the molecular mechanisms driving tumor formation. This can be accomplished by 
      obtaining a more complete description of the genes that contribute to cancer. We 
      previously described an approach using the Sleeping Beauty (SB) transposon system 
      to model hematopoietic malignancies in mice. Here, we describe modifications of 
      the SB system that provide additional flexibility in generating mouse models of 
      cancer. First, we describe a Cre-inducible SBase allele, RosaSBase(LsL), that 
      allows the restriction of transposon mutagenesis to a specific tissue of 
      interest. This allele was used to generate a model of germinal center B-cell 
      lymphoma by activating SBase expression with an Aid-Cre allele. In a second 
      approach, a novel transposon was generated, T2/Onc3, in which the CMV 
      enhancer/chicken beta-actin promoter drives oncogene expression. When combined 
      with ubiquitous SBase expression, the T2/Onc3 transposon produced nearly 200 
      independent tumors of more than 20 different types in a cohort of 62 mice. 
      Analysis of transposon insertion sites identified novel candidate genes, 
      including Zmiz1 and Rian, involved in squamous cell carcinoma and hepatocellular 
      carcinoma, respectively. These novel alleles provide additional tools for the SB 
      system and provide some insight into how this mutagenesis system can be 
      manipulated to model cancer in mice.
FAU - Dupuy, Adam J
AU  - Dupuy AJ
AD  - Department of Anatomy and Cell Biology, Center for Bioinformatics, Computational 
      Biology and Biomedical Engineering, Roy J and Lucille A Carver College of 
      Medicine, University of Iowa, Iowa City, Iowa 52242, USA. adam-dupuy@uiowa.edu
FAU - Rogers, Laura M
AU  - Rogers LM
FAU - Kim, Jinsil
AU  - Kim J
FAU - Nannapaneni, Kishore
AU  - Nannapaneni K
FAU - Starr, Timothy K
AU  - Starr TK
FAU - Liu, Pentao
AU  - Liu P
FAU - Largaespada, David A
AU  - Largaespada DA
FAU - Scheetz, Todd E
AU  - Scheetz TE
FAU - Jenkins, Nancy A
AU  - Jenkins NA
FAU - Copeland, Neal G
AU  - Copeland NG
LA  - eng
GR  - R01 CA113636/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20091006
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (DNA Transposable Elements)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (Rian protein, mouse)
RN  - 0 (Zimp10 protein, mouse)
RN  - 0 (enhanced green fluorescent protein)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - EC 2.7.7.- (Cre recombinase)
RN  - EC 2.7.7.- (Integrases)
SB  - IM
MH  - Animals
MH  - Carcinoma, Hepatocellular/*genetics/pathology
MH  - DNA Transposable Elements/*genetics
MH  - *Disease Models, Animal
MH  - Female
MH  - Green Fluorescent Proteins/genetics/metabolism
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - Integrases/metabolism
MH  - Intracellular Signaling Peptides and Proteins/genetics/metabolism
MH  - Liver Neoplasms, Experimental/*genetics/pathology
MH  - Lymphoma, B-Cell/*genetics/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C3H
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Monte Carlo Method
MH  - Mutagenesis, Insertional
MH  - Mutation/genetics
MH  - Nuclear Proteins/genetics/metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - RNA-Binding Proteins
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Skin Neoplasms/*genetics/pathology
PMC - PMC3700628
MID - NIHMS141347
EDAT- 2009/10/08 06:00
MHDA- 2009/12/16 06:00
PMCR- 2013/07/03
CRDT- 2009/10/08 06:00
PHST- 2009/10/08 06:00 [entrez]
PHST- 2009/10/08 06:00 [pubmed]
PHST- 2009/12/16 06:00 [medline]
PHST- 2013/07/03 00:00 [pmc-release]
AID - 0008-5472.CAN-09-1135 [pii]
AID - 10.1158/0008-5472.CAN-09-1135 [doi]
PST - ppublish
SO  - Cancer Res. 2009 Oct 15;69(20):8150-6. doi: 10.1158/0008-5472.CAN-09-1135. Epub 
      2009 Oct 6.