PUBLICATION

The INT6 Cancer Gene and MEK Signaling Pathways Converge during Zebrafish Development

Authors
Grzmil, M., Whiting, D., Maule, J., Anastasaki, C., Amatruda, J.F., Kelsh, R.N., Norbury, C.J., and Patton, E.E.
ID
ZDB-PUB-071001-14
Date
2007
Source
PLoS One   2(9): e959 (Journal)
Registered Authors
Amatruda, James F., Kelsh, Robert, Maule, John, Patton, E. Elizabeth
Keywords
Embryos, Zebrafish, Developmental signaling, Cartilage, MAPK signaling cascades, ERK signaling cascade, Small interfering RNAs, Oncogenic signaling
MeSH Terms
  • Eukaryotic Initiation Factor-3/genetics*
  • Eukaryotic Initiation Factor-3/physiology
  • Immunoblotting
  • MAP Kinase Kinase 1/genetics
  • MAP Kinase Kinase 1/metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism
  • Cell Line, Tumor
  • RNA, Small Interfering/genetics
  • MAP Kinase Signaling System/genetics*
  • MAP Kinase Signaling System/physiology
  • Animals
  • Humans
  • Zebrafish/embryology
  • Zebrafish/genetics*
  • Zebrafish/growth & development
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/physiology
(all 19)
PubMed
17895999 Full text @ PLoS One
CTD
17895999
Abstract
BACKGROUND: Int-6 (integration site 6) was identified as an oncogene in a screen of tumorigenic mouse mammary tumor virus (MMTV) insertions. INT6 expression is altered in human cancers, but the precise role of disrupted INT6 in tumorigenesis remains unclear, and an animal model to study Int-6 physiological function has been lacking. PRINCIPAL FINDINGS: Here, we create an in vivo model of Int6 function in zebrafish, and through genetic and chemical-genetic approaches implicate Int6 as a tissue-specific modulator of MEK-ERK signaling. We find that Int6 is required for normal expression of MEK1 protein in human cells, and for Erk signaling in zebrafish embryos. Loss of either Int6 or Mek signaling causes defects in craniofacial development, and Int6 and Erk-signaling have overlapping domains of tissue expression. SIGNIFICANCE: Our results provide new insight into the physiological role of vertebrate Int6, and have implications for the treatment of human tumors displaying altered INT6 expression.
Genes / Markers
Figures
Figure Gallery (8 images)
Show all Figures
Expression
Phenotype
Fish Conditions Stage Phenotype Figure
WT + MO1-eif3eastandard conditionsLong-pec to Protruding-mouth
WT + MO1-eif3eastandard conditionsLong-pec to Protruding-mouth
WT + MO1-eif3eastandard conditionsLong-pec to Protruding-mouth
WT + MO1-eif3eastandard conditionsLong-pec to Protruding-mouth
WT + MO1-eif3eastandard conditionsDay 5
WT + MO1-eif3eastandard conditionsDay 5
WT + MO1-eif3eastandard conditionsDay 5
WT + MO1-eif3eastandard conditionsDay 5
WT + MO1-eif3eastandard conditionsDay 5
WT + MO1-eif3eastandard conditionsDay 5
1 - 10 of 16
Show
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
hi2470TgTransgenic Insertion
1 - 1 of 1
Show
Human Disease / Model
No data available
Sequence Targeting Reagents
Target Reagent Reagent Type
eif3eaMO1-eif3eaMRPHLNO
1 - 1 of 1
Show
Fish
Antibodies
Orthology
No data available
Engineered Foreign Genes
No data available
Mapping
Your Input Welcome
We welcome your input and comments. Please use this form to recommend updates to the information in ZFIN. We appreciate as much detail as possible and references as appropriate. We will review your comments promptly.
Citation
Grzmil, M., Whiting, D., Maule, J., Anastasaki, C., Amatruda, J.F., Kelsh, R.N., Norbury, C.J., and Patton, E.E. (2007) The INT6 Cancer Gene and MEK Signaling Pathways Converge during Zebrafish Development. PLoS One. 2(9):e959.