TY - JOUR
T1 - The INT6 Cancer Gene and MEK Signaling Pathways Converge during Zebrafish Development
AU - Grzmil, Michal
AU - Whiting, Danny
AU - Maule, John
AU - Anastasaki, Corina
AU - Amatruda, James F.
AU - Kelsh, Robert N.
AU - Norbury, Chris J.
AU - Patton, E. Elizabeth
PY - 2007
Y1 - 2007
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=52249108555&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0000959
DO - 10.1371/journal.pone.0000959
M3 - Article
C2 - 17895999
AN - SCOPUS:52249108555
SN - 1932-6203
VL - 2
JO - PloS one
JF - PloS one
IS - 9
M1 - e0000959
ER -