title: Possible aryl hydrocarbon receptor-independent pathway of 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced antiproliferative response in human breast cancer cells.
abstract: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a ligand with high affinity for the aryl hydrocarbon receptor (AhR). It suppresses 17β-estradiol (E2)-induced cell proliferation in human breast cancer cells. Although it has been theorized that the AhR is involved in TCDD-induced antiestrogenic activity and antiproliferation in human breast cancer cells, some evidence suggests that these activities of chlorinated aromatic compounds also occur by AhR-independent pathways. Here, we investigated the possibility of TCDD-induced antiproliferative responses in human breast cancer cells through AhR-independent pathways. Compared with that in vehicle-treated controls, DNA synthesis was significantly suppressed in MCF-7 cells and ZR75-1 cells treated with TCDD at a very low concentration (0.01 nM), whereas that in human ovarian carcinoma OVCAR3 cells, human cervical carcinoma HeLa cells and human choriocarcinoma JEG-3 cells was unaffected, even by exposure to 10 nM TCDD. The suppression induced by TCDD was not associated with the estrogen receptor α-signaling pathway. Another AhR agonist, 3,3',4,4',5-pentachlorobiphenyl, had no effect on DNA synthesis in MCF-7 cells at concentrations high enough to induce the transactivation function of the AhR. Furthermore, in MCF-7 cells, knockdown of the AhR by RNA interference had no effect on TCDD-induced antiproliferation. These findings suggest that the principal pathways of TCDD-induced antiproliferation in breast cancer cells are not AhR dependent.
authors.affiliation: Laboratory of Hygienic Chemistry and Molecular Toxicology, Gifu Pharmaceutical University, 1-25-4 Daigaku-Nishi, Gifu, Gifu 501-1196, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yoshioka
authors.forename: Youhei
authors.initials: Y
authors.lastname: Hiromori
authors.forename: Akira
authors.initials: A
authors.lastname: Aoki
authors.forename: Tomoki
authors.initials: T
authors.lastname: Kimura
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Fujii-Kuriyama
authors.forename: Hisamitsu
authors.initials: H
authors.lastname: Nagase
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Nakanishi
mesh_terms: D000199:Actins / Q000096:biosynthesis; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000096:biosynthesis / Q000235:genetics; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D017931:DNA Primers / Q000494:pharmacology; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D006367:HeLa Cells; D006801:Humans; D010957:Plasmids / Q000235:genetics; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D034622:RNA Interference; D060888:Real-Time Polymerase Chain Reaction; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000502:physiology*; D011960:Receptors, Estrogen / Q000096:biosynthesis / Q000235:genetics; D013936:Thymidine / Q000378:metabolism; D014162:Transfection
chemical_list: C497396:ARNT protein, human; D000199:Actins; D017931:DNA Primers; D018076:DNA, Complementary; D047628:Estrogen Receptor alpha; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D011960:Receptors, Estrogen; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D004958:Estradiol; D013936:Thymidine