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 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.
Andersson
Patrik
P
Department of Cell and Molecular Biology, Institute of Environmental Medicine, Karolinska Institute, S-171 77 Stockholm, Sweden.
McGuire
Jacqueline
J
Rubio
Carlos
C
Gradin
Katarina
K
Whitelaw
Murray L
ML
Pettersson
Sven
S
Hanberg
Annika
A
Poellinger
Lorenz
L
D000818:Animals; D016466:CHO Cells; D002273:Carcinogens / Q000494:pharmacology; D003001:Cloning, Molecular; D006224:Cricetinae; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D007414:Intestinal Neoplasms / Q000235:genetics / Q000473:pathology / Q000556:secondary; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D013950:Thymus Gland / Q000201:enzymology; D014162:Transfection
D002273:Carcinogens; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D011994:Recombinant Proteins; D019363:Cytochrome P-450 CYP1A1