Effect of dioxin and 17β-estradiol on the expression of cytochrome P450 1A1 gene via an estrogen receptor dependent pathway in cellular and xenografted models

Abstract

Cytochrome P450 (CYP) 1A1 plays a major role in the metabolic activation of procarcinogens to carcinogens via aryl hydrocarbon receptor (AhR) pathway. Especially, 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) is known as an agonist of AhR. In estrogen responsive cancers, 17β‐estradiol (E2) may influence on AhR dependent expression of CYP1 family via the interaction between estrogen receptor (ER) and AhR. In the present study, the effect of E2/ER on the expression of AhR and CYP1A1 genes was investigated for MCF‐7 clonal variant (MCF‐7 CV) breast cancer cells expressing ER. In reverse transcription‐PCR and Western blot analysis, mRNA expression level of AhR was not altered, but its protein expression level was increased by TCDD or E2. The transcriptional and translational levels of CYP1A1 appeared to be increased by TCDD or E2. The increased expression of AhR and CYP1A1 induced by E2 was restored to the control level by the co‐treatment of ICI 182,780, indicating that E2 induced the protein expression levels of AhR and CYP1A1 like TCDD via an ER dependent pathway. In an in vivo xenograft mouse model transplanted with MCF‐7 CV cells, the protein expression levels of AhR and CYP1A1 of tumor masses were also increased by E2 or TCDD. Taken together, these results indicate that E2 may promote AhR dependent expression of CYP1A1 via ER dependent pathway in MCF‐7 CV cells expressing ER in the absence of TCDD, an agonist of AhR. The relevance of E2 and ER in CYP1A1 activation of estrogen responsive cancers may be targeted for developing more effective cancer treatments.

Alternaria alternata Toxins Synergistically Activate the Aryl Hydrocarbon Receptor Pathway In Vitro

“…Exhibiting a roughly 7-fold induction of EROD enzyme activity, 1 µM B[a]P served as a positive control for AhR signalling pathway activation ( Figure 2 a). In contrast, E2 showed no estrogen-related induction of CYP 1 activity in our MCF-7 cell model ( Figure 2 a), which was suggested in a previously published study [ 61 ]. Both, the CE and the RE (stripped from the two perylene quinones ATX-II and STTX-III), led to dose-dependent enhancements of CYP 1A1 activity ( Figure 2 a).…”

AhR-activating pesticides increase the bovine ABCG2 efflux activity in MDCKII-bABCG2 cells

“…However, in previous EROD studies, no alteration of CYP1A enzyme activity was detected in MDCKII-bABCG2 cells [ 29 ]. Post-transcriptional regulation by dynamic RNA modification may explain why the down-regulation of CYP1A1 mRNA by PCB101 does not decrease CYP1A enzyme activity [ 59 ].…”

Chronic Low-Dose Exposure to Xenoestrogen Ambient Air Pollutants and Breast Cancer Risk: XENAIR Protocol for a Case-Control Study Nested Within the French E3N Cohort

“…Current evidence on the role of genetic susceptibility (polymorphisms) related to exposure to ambient air pollution remains limited. Previous epidemiological studies have reported interactions between genetic polymorphisms and some pollutants [ 53 , 54 ]. Saintot et al reported that women carrying the Val CYP1B1 allele and who had lived near a waste incinerator for more than 10 years had a greater risk of breast cancer than those with the Leu/Leu genotype and had never been exposed [ 55 ].…”