A Constitutively Active Dioxin/Aryl Hydrocarbon Receptor Induces Stomach Tumors

The dioxin/aryl hydrocarbon receptor (AhR) functions as a ligand-activated transcription factor regulating transcription of a battery of genes encoding xenobiotic metabolizing enzymes. Known receptor ligands are environmental pollutants including polycyclic aromatic hydrocarbons and polychlorinated...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2002-07, Vol.99 (15), p.9990-9995
Main Authors: Andersson, Patrik, McGuire, Jacqueline, Rubio, Carlos, Gradin, Katarina, Whitelaw, Murray L., Pettersson, Sven, Hanberg, Annika, Poellinger, Lorenz
Format: Article
Language:English
Subjects:
Animals
Biological Sciences
Carcinogens - pharmacology
Cell growth
CHO Cells
Cloning, Molecular
Cricetinae
Cytochrome P-450 CYP1A1 - genetics
Gene Expression Regulation, Developmental
Intestinal Neoplasms - genetics
Intestinal Neoplasms - pathology
Intestinal Neoplasms - secondary
Ligands
Liver
Liver - enzymology
Male
Messenger RNA
Mice
Mice, Inbred C57BL
Mice, Inbred CBA
Mucosa
Polychlorinated Dibenzodioxins - pharmacology
Receptors
Receptors, Aryl Hydrocarbon - genetics
Receptors, Aryl Hydrocarbon - metabolism
Recombinant Proteins - metabolism
RNA
Stomach
Stomach Neoplasms - genetics
Stomach Neoplasms - pathology
Thymus Gland - enzymology
Transfection
Tumors
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Summary:The dioxin/aryl hydrocarbon receptor (AhR) functions as a ligand-activated transcription factor regulating transcription of a battery of genes encoding xenobiotic metabolizing enzymes. Known receptor ligands are environmental pollutants including polycyclic aromatic hydrocarbons and polychlorinated dioxins. Loss-of-function (gene-disruption) studies in mice have demonstrated that the AhR is involved in toxic effects of dioxins but have not yielded unequivocal results concerning the physiological function of the receptor. Gain-of-function studies therefore were performed to unravel the biological functions of the AhR. A constitutively active AhR expressed in transgenic mice reduced the life span of the mice and induced tumors in the glandular part of the stomach, demonstrating the oncogenic potential of the AhR and implicating the receptor in regulation of cell proliferation.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.152706299