PMID- 23821038
OWN - NLM
STAT- MEDLINE
DCOM- 20130904
LR  - 20220317
IS  - 1477-9129 (Electronic)
IS  - 0950-1991 (Print)
IS  - 0950-1991 (Linking)
VI  - 140
IP  - 14
DP  - 2013 Jul
TI  - Zebrafish rhabdomyosarcoma reflects the developmental stage of oncogene 
      expression during myogenesis.
PG  - 3040-50
LID - 10.1242/dev.087858 [doi]
AB  - Rhabdomyosarcoma is a pediatric malignancy thought to arise from the uncontrolled 
      proliferation of myogenic cells. Here, we have generated models of 
      rhabdomyosarcoma in the zebrafish by inducing oncogenic KRAS(G12D) expression at 
      different stages during muscle development. Several zebrafish promoters were 
      used, including the cdh15 and rag2 promoters, which drive gene expression in 
      early muscle progenitors, and the mylz2 promoter, which is expressed in 
      differentiating myoblasts. The tumors that developed differed in their ability to 
      recapitulate normal myogenesis. cdh15:KRAS(G12D) and rag2:KRAS(G12D) fish 
      developed tumors that displayed an inability to complete muscle differentiation 
      as determined by histological appearance and gene expression analyses. By 
      contrast, mylz2:KRAS(G12D) tumors more closely resembled mature skeletal muscle 
      and were most similar to well-differentiated human rhabdomyosarcoma in terms of 
      gene expression. mylz2:KRAS(G12D) fish showed significantly improved survival 
      compared with cdh15:KRAS(G12D) and rag2:KRAS(G12D) fish. Tumor-propagating 
      activity was enriched in myf5-expressing cell populations within all of the tumor 
      types. Our results demonstrate that oncogenic KRAS(G12D) expression at different 
      stages during muscle development has profound effects on the ability of tumor 
      cells to recapitulate normal myogenesis, altering the tumorigenic capability of 
      these cells.
FAU - Storer, Narie Y
AU  - Storer NY
AD  - Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital 
      and Dana-Farber Cancer Institute, Boston, MA 02115, USA.
FAU - White, Richard M
AU  - White RM
FAU - Uong, Audrey
AU  - Uong A
FAU - Price, Emily
AU  - Price E
FAU - Nielsen, G Petur
AU  - Nielsen GP
FAU - Langenau, David M
AU  - Langenau DM
FAU - Zon, Leonard I
AU  - Zon LI
LA  - eng
GR  - R01 CA154923/CA/NCI NIH HHS/United States
GR  - P30 DK049216/DK/NIDDK NIH HHS/United States
GR  - T32 GM007753/GM/NIGMS NIH HHS/United States
GR  - R01 CA103846/CA/NCI NIH HHS/United States
GR  - R01CA103846/CA/NCI NIH HHS/United States
GR  - T32GM007753/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - England
TA  - Development
JT  - Development (Cambridge, England)
JID - 8701744
RN  - 0 (Cadherins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (KRAS protein, human)
RN  - 0 (Myosin Light Chains)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RAG2 protein, zebrafish)
RN  - 0 (Zebrafish Proteins)
RN  - 0 (cadherin 15, zebrafish)
RN  - 0 (myosin light chain 2)
RN  - EC 3.6.1.- (Cardiac Myosins)
RN  - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
RN  - EC 3.6.5.2 (ras Proteins)
SB  - IM
MH  - Animals
MH  - Animals, Genetically Modified
MH  - Cadherins/genetics
MH  - Cardiac Myosins/genetics
MH  - DNA-Binding Proteins/genetics
MH  - *Disease Models, Animal
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - *Muscle Development
MH  - Myosin Light Chains/genetics
MH  - Promoter Regions, Genetic
MH  - Proto-Oncogene Proteins/genetics
MH  - Proto-Oncogene Proteins p21(ras)
MH  - Rhabdomyosarcoma/*genetics
MH  - Stem Cells/metabolism
MH  - Zebrafish/embryology/genetics/metabolism
MH  - Zebrafish Proteins/genetics
MH  - ras Proteins/genetics
PMC - PMC3699286
OTO - NOTNLM
OT  - Muscle
OT  - Rhabdomyosarcoma
OT  - Zebrafish
EDAT- 2013/07/04 06:00
MHDA- 2013/09/05 06:00
PMCR- 2014/07/15
CRDT- 2013/07/04 06:00
PHST- 2013/07/04 06:00 [entrez]
PHST- 2013/07/04 06:00 [pubmed]
PHST- 2013/09/05 06:00 [medline]
PHST- 2014/07/15 00:00 [pmc-release]
AID - 140/14/3040 [pii]
AID - 10.1242/dev.087858 [doi]
PST - ppublish
SO  - Development. 2013 Jul;140(14):3040-50. doi: 10.1242/dev.087858.