2,3,7,8-Tetrachlorodibenzo-para-dioxin increases aromatase (CYP19) mRNA stability in MCF-7 cells.
Dioxins are industrial pollutants that can be bio-accumulative in our food chain. Humans can be exposed to this class of pollutant through contaminated food, air, drinking water, etc. Displaying both pro- and anti-estrogenic properties, these pollutants are also known as endocrine disruptors. The link between breast cancer and TCDD exposure has not been resolved, although TCDD is classified as 'known human carcinogen'. Estrogen is a documented risk factor for breast carcinogenesis. In the present study, effect of 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD) on estrogen synthesis was investigated in the breast cancer cells MCF-7. Our results showed that TCDD increased the aromatase activity in a time- and dose-dependent manner. Real-time PCR and western blot analysis verified the induced expression by 2-3-fold; however, gene reporter assay revealed that the promoter activity of exons I.3 and II was not elevated. Further investigation indicated that TCDD slowed down the CYP19 mRNA degradation with concurrent activation of ERK. The ERK inhibitor U0126 could reverse the extended stability of the transcripts. In summary this study demonstrated that TCDD might induce a post-transcriptional regulatory mechanism of gene expression in breast cancer cells.
Chan
Ming Yan
MY
Department of Biochemistry, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong.
Huang
Hui
H
Leung
Lai K
LK
D000954:Antigens, Surface / Q000378:metabolism; D001141:Aromatase / Q000096:biosynthesis / Q000235:genetics*; D015153:Blotting, Western; D002070:Butadienes / Q000494:pharmacology; D045744:Cell Line, Tumor; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D004790:Enzyme Induction / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D006801:Humans; D009570:Nitriles / Q000494:pharmacology; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology / Q000633:toxicity*; D011401:Promoter Regions, Genetic / Q000235:genetics; D020871:RNA Stability / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism
D000954:Antigens, Surface; D002070:Butadienes; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D009570:Nitriles; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C113580:U 0126; D001141:Aromatase; D048049:Extracellular Signal-Regulated MAP Kinases