Aryl hydrocarbon receptor agonists directly activate estrogen receptor alpha in MCF-7 breast cancer cells.
The aryl hydrocarbon receptor (AhR) binds with high affinity to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related halogenated aromatics, but also binds with lower affinity to structurally diverse exogenous and endogenous chemicals. One study reported that 3-methylcholanthrene (3MC) activated the estrogen receptor (ER) through the AhR, which acts as co-regulatory protein, whereas a recent report showed that 3MC directly bound and activated ERalpha. This study also shows that the AhR agonists benzo[a]pyrene, 3,3',4,4'-tetrachlorobiphenyl, chrysin, 6-methyl-1,3,8-trichlorodibenzofuran, and 3,3'-diindolylmethane also induce ERalpha-dependent transactivation. Moreover, in chromatin immunoprecipitation assays, these compounds induce binding of AhR and ERalpha to the CYP1A1 and pS2 gene promoters, which is consistent with their activities as both selective AhR modulators (SAhRMs) and selective ER modulators (SERMs).
Liu
Shengxi
S
Institute of Biosciences and Technology, Texas A&M University Health Science Center, 2121 W. Holcombe Blvd., Houston, TX 77030-3303, USA.
Abdelrahim
Maen
M
Khan
Shaheen
S
Ariazi
Eric
E
Jordan
V Craig
VC
Safe
Stephen
S
D001564:Benzo(a)pyrene / Q000494:pharmacology; D001572:Benzofurans / Q000494:pharmacology; D001665:Binding Sites; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D019363:Cytochrome P-450 CYP1A1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000187:drug effects* / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008024:Ligands; D008748:Methylcholanthrene / Q000494:pharmacology; D011078:Polychlorinated Biphenyls / Q000494:pharmacology; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D053766:Presenilin-2 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists* / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship
D001572:Benzofurans; D047628:Estrogen Receptor alpha; D005419:Flavonoids; D007211:Indoles; D008024:Ligands; D000072317:Polychlorinated Dibenzodioxins; D053766:Presenilin-2; D018336:Receptors, Aryl Hydrocarbon; C054923:6-methyl-1,3,8-trichlorodibenzofuran; D001564:Benzo(a)pyrene; C043561:chrysin; D008748:Methylcholanthrene; D011078:Polychlorinated Biphenyls; D019363:Cytochrome P-450 CYP1A1; C016392:3,3'-diindolylmethane; C028451:3,4,3',4'-tetrachlorobiphenyl