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

Cited 15 time in scopus
Metadata Downloads
Title
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
Author(s)
R E Go; K A Hwang; C W Kim; Yong Sub Byun; Ki Hoan Nam; K C Choi
Bibliographic Citation
Environmental Toxicology, vol. 32, no. 10, pp. 2225-2233
Publication Year
2017
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.
Keyword
17 β-estradiolbreast cancerCYP1A1dioxinxenograft model
ISSN
1520-4081
Publisher
Wiley
DOI
http://dx.doi.org/10.1002/tox.22438
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of National Bio-Infrastructure > Laboratory Animal Resource & Research Center > 1. Journal Articles
Files in This Item:
  • There are no files associated with this item.


Items in OpenAccess@KRIBB are protected by copyright, with all rights reserved, unless otherwise indicated.