PMID- 17895999
OWN - NLM
STAT- MEDLINE
DCOM- 20080924
LR  - 20220129
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 2
IP  - 9
DP  - 2007 Sep 26
TI  - The INT6 cancer gene and MEK signaling pathways converge during zebrafish 
      development.
PG  - e959
LID - e959
AB  - 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.
FAU - Grzmil, Michal
AU  - Grzmil M
AD  - Sir William Dunn School of Pathology, University of Oxford, Oxford, United 
      Kingdom.
FAU - Whiting, Danny
AU  - Whiting D
FAU - Maule, John
AU  - Maule J
FAU - Anastasaki, Corina
AU  - Anastasaki C
FAU - Amatruda, James F
AU  - Amatruda JF
FAU - Kelsh, Robert N
AU  - Kelsh RN
FAU - Norbury, Chris J
AU  - Norbury CJ
FAU - Patton, E Elizabeth
AU  - Patton EE
LA  - eng
GR  - A7791/CRUK_/Cancer Research UK/United Kingdom
GR  - G120/875/MRC_/Medical Research Council/United Kingdom
GR  - MC_PC_U127585840/MRC_/Medical Research Council/United Kingdom
GR  - MC_U127585840/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070926
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Eukaryotic Initiation Factor-3)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Zebrafish Proteins)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 1)
RN  - EC 2.7.12.2 (MAP2K1 protein, human)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - Eukaryotic Initiation Factor-3/*genetics/physiology
MH  - Humans
MH  - Immunoblotting
MH  - MAP Kinase Kinase 1/genetics/metabolism
MH  - MAP Kinase Signaling System/*genetics/physiology
MH  - RNA, Messenger/genetics/metabolism
MH  - RNA, Small Interfering/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Zebrafish/embryology/*genetics/growth & development
MH  - Zebrafish Proteins/*genetics/physiology
PMC - PMC1978538
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2007/09/27 09:00
MHDA- 2008/09/25 09:00
PMCR- 2007/09/26
CRDT- 2007/09/27 09:00
PHST- 2007/08/03 00:00 [received]
PHST- 2007/09/02 00:00 [accepted]
PHST- 2007/09/27 09:00 [pubmed]
PHST- 2008/09/25 09:00 [medline]
PHST- 2007/09/27 09:00 [entrez]
PHST- 2007/09/26 00:00 [pmc-release]
AID - 07-PONE-RA-01926R1 [pii]
AID - 10.1371/journal.pone.0000959 [doi]
PST - epublish
SO  - PLoS One. 2007 Sep 26;2(9):e959. doi: 10.1371/journal.pone.0000959.