A constitutively active dioxin/aryl hydrocarbon receptor induces stomach tumors

被引:242
作者
Andersson, P
McGuire, J
Rubio, C
Gradin, K
Whitelaw, ML
Pettersson, S
Hanberg, A
Poellinger, L [1 ]
机构
[1] Karolinska Inst, Dept Cell & Mol Biol, S-17177 Stockholm, Sweden
[2] Karolinska Inst, Inst Environm Med, S-17177 Stockholm, Sweden
[3] Karolinska Inst, Dept Oncol Pathol, S-17177 Stockholm, Sweden
[4] Karolinska Inst, Microbiol & Tumor Biol Ctr, S-17177 Stockholm, Sweden
[5] Univ Adelaide, Dept Biochem, Adelaide, SA 5000, Australia
关键词
D O I
10.1073/pnas.152706299
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:9990 / 9995
页数:6
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