title: The INT6 cancer gene and MEK signaling pathways converge during zebrafish development.
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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom.
authors: Michal
authors: M
authors: Grzmil
authors: Danny
authors: D
authors: Whiting
authors: John
authors: J
authors: Maule
authors: Corina
authors: C
authors: Anastasaki
authors: James F
authors: JF
authors: Amatruda
authors: Robert N
authors: RN
authors: Kelsh
authors: Chris J
authors: CJ
authors: Norbury
authors: E Elizabeth
authors: EE
authors: Patton
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D039621:Eukaryotic Initiation Factor-3 / Q000235:genetics* / Q000502:physiology; D006801:Humans; D015151:Immunoblotting; D048369:MAP Kinase Kinase 1 / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000235:genetics* / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015027:Zebrafish / Q000196:embryology / Q000235:genetics* / Q000254:growth & development; D029961:Zebrafish Proteins / Q000235:genetics* / Q000502:physiology
chemical_list: D039621:Eukaryotic Initiation Factor-3; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D029961:Zebrafish Proteins; D048369:MAP Kinase Kinase 1; C482125:MAP2K1 protein, human