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

Michal Grzmil, Danny Whiting, John Maule, Corina Anastasaki, James F. Amatruda, Robert N. Kelsh, Chris J. Norbury, E. Elizabeth Patton

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere0000959
JournalPLoS One
Volume2
Issue number9
DOIs
StatePublished - 2007

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Neoplasm Genes
Mitogen-Activated Protein Kinase Kinases
Zebrafish
Danio rerio
Genes
Mouse mammary tumor virus
neoplasms
Oncogenes
Vertebrates
Tumors
Neoplasms
Carcinogenesis
genes
Embryonic Structures
Animal Models
oncogenes
Tissue
carcinogenesis
embryo (animal)
protein synthesis

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Grzmil, M., Whiting, D., Maule, J., Anastasaki, C., Amatruda, J. F., Kelsh, R. N., ... Patton, E. E. (2007). The INT6 Cancer Gene and MEK Signaling Pathways Converge during Zebrafish Development. PLoS One, 2(9), [e0000959]. https://doi.org/10.1371/journal.pone.0000959

The INT6 Cancer Gene and MEK Signaling Pathways Converge during Zebrafish Development. / Grzmil, Michal; Whiting, Danny; Maule, John; Anastasaki, Corina; Amatruda, James F.; Kelsh, Robert N.; Norbury, Chris J.; Patton, E. Elizabeth.

In: PLoS One, Vol. 2, No. 9, e0000959, 2007.

Research output: Contribution to journalArticle

Grzmil, M, Whiting, D, Maule, J, Anastasaki, C, Amatruda, JF, Kelsh, RN, Norbury, CJ & Patton, EE 2007, 'The INT6 Cancer Gene and MEK Signaling Pathways Converge during Zebrafish Development', PLoS One, vol. 2, no. 9, e0000959. https://doi.org/10.1371/journal.pone.0000959
Grzmil M, Whiting D, Maule J, Anastasaki C, Amatruda JF, Kelsh RN et al. The INT6 Cancer Gene and MEK Signaling Pathways Converge during Zebrafish Development. PLoS One. 2007;2(9). e0000959. https://doi.org/10.1371/journal.pone.0000959
Grzmil, Michal ; Whiting, Danny ; Maule, John ; Anastasaki, Corina ; Amatruda, James F. ; Kelsh, Robert N. ; Norbury, Chris J. ; Patton, E. Elizabeth. / The INT6 Cancer Gene and MEK Signaling Pathways Converge during Zebrafish Development. In: PLoS One. 2007 ; Vol. 2, No. 9.
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