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The INT6 Cancer Gene and MEK Signaling Pathways Converge during Zebrafish Development
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 physio...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2007
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1978538/ https://www.ncbi.nlm.nih.gov/pubmed/17895999 http://dx.doi.org/10.1371/journal.pone.0000959 |
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author | Grzmil, Michal Whiting, Danny Maule, John Anastasaki, Corina Amatruda, James F. Kelsh, Robert N. Norbury, Chris J. Patton, E. Elizabeth |
author_facet | Grzmil, Michal Whiting, Danny Maule, John Anastasaki, Corina Amatruda, James F. Kelsh, Robert N. Norbury, Chris J. Patton, E. Elizabeth |
author_sort | Grzmil, Michal |
collection | PubMed |
description | 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. |
format | Text |
id | pubmed-1978538 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-19785382007-09-26 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 PLoS One Research Article 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. Public Library of Science 2007-09-26 /pmc/articles/PMC1978538/ /pubmed/17895999 http://dx.doi.org/10.1371/journal.pone.0000959 Text en Grzmil et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article 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 |
title | The INT6 Cancer Gene and MEK Signaling Pathways Converge during Zebrafish Development |
title_full | The INT6 Cancer Gene and MEK Signaling Pathways Converge during Zebrafish Development |
title_fullStr | The INT6 Cancer Gene and MEK Signaling Pathways Converge during Zebrafish Development |
title_full_unstemmed | The INT6 Cancer Gene and MEK Signaling Pathways Converge during Zebrafish Development |
title_short | The INT6 Cancer Gene and MEK Signaling Pathways Converge during Zebrafish Development |
title_sort | int6 cancer gene and mek signaling pathways converge during zebrafish development |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1978538/ https://www.ncbi.nlm.nih.gov/pubmed/17895999 http://dx.doi.org/10.1371/journal.pone.0000959 |
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