A constitutively active dioxin/aryl hydrocarbon receptor induces stomach tumors

Date

2002

Authors

Andersson, P.
McGuire, J.
Rubio, C.
Gradin, K.
Whitelaw, M.
Pettersson, S.
Hanberg, A.
Poellinger, L.

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Journal article

Citation

Proceedings of the National Academy of Sciences of USA, 2002; 99(15):9990-9995

Statement of Responsibility

Patrik Andersson, Jacqueline McGuire, Carlos Rubio, Katarina Gradin, Murray L. Whitelaw, Sven Pettersson, Annika Hanberg, and Lorenz Poellinger

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Abstract

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.

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Published online before print July 9, 2002

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Copyright © 2002 by the National Academy of Sciences

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