Inhibition of E2-induced expression of BRCA1 by persistent organochlorines
| Autor: | Irene M. Gjermandsen, Thomas Rattenborg, Eva Cecilie Bonefeld-Jørgensen |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
Cyclin-Dependent Kinase Inhibitor p21
Polychlorinated Dibenzodioxins Tumor suppressor gene polychlorinated biphenyls Genes BRCA1 Gene Expression Estrogen receptor Biology Cyclins Gene expression Tumor Cells Cultured medicine Humans RNA Messenger Northern blot Promoter Regions Genetic skin and connective tissue diseases Gene Toxaphene Medicine(all) Reporter gene Dose-Response Relationship Drug Estradiol Cancer tetrachlorodibenzo-p-dioxin BRCA1 Blotting Northern medicine.disease Blot Cancer research Female Research Article estrogen receptor |
| Zdroj: | Rattenborg, T, Gjermandsen, I & Bonefeld-Jørgensen, E C 2002, ' Inhibition of E2-induced expression of BRCA1 by persistent organochlorines ', Breast Cancer Research (Online Edition), vol. 4, no. 6, pp. R12 . https://doi.org/10.1186/bcr461 Breast Cancer Research |
| ISSN: | 1465-542X |
| DOI: | 10.1186/bcr461 |
| Popis: | Udgivelsesdato: Jul 24 BACKGROUND: Environmental persistent organochlorines (POCs) biomagnify in the food chain, and the chemicals are suspected of being involved in a broad range of human malignancies. It is speculated that some POCs that can interfere with estrogen receptor-mediated responses are involved in the initiation and progression of human breast cancer. The tumor suppressor gene BRCA1 plays a role in cell-cycle control, in DNA repair, and in genomic stability, and it is often downregulated in sporadic mammary cancers. The aim of the present study was to elucidate whether POCs have the potential to alter the expression of BRCA1. METHODS: Using human breast cancer cell lines MCF-7 and MDA-MB-231, the effect on BRCA1 expression of chemicals belonging to different classes of organochlorine chemicals (the pesticide toxaphene, 2,3,7,8-tetrachlorodibenzo-p-dioxin, and three polychlorinated biphenyls [PCB#138, PCB#153 and PCB#180]) was measured by a reporter gene construct carrying 267 bp of the BRCA1 promoter. A twofold concentration range was analyzed in MCF-7, and the results were supported by northern blot analysis of BRCA1 mRNA using the highest concentrations of the chemicals. RESULTS: All three polychlorinated biphenyls and 2,3,7,8-tetrachlorodibenzo-p-dioxin reduced 17beta-estradiol (E2)-induced expression as well as basal reporter gene expression in both cell lines, whereas northern blot analysis only revealed a downregulation of E2-induced BRCA1 mRNA expression in MCF-7 cells. Toxaphene, like E2, induced BRCA1 expression in MCF-7. CONCLUSION: The present study shows that some POCs have the capability to alter the expression of the tumor suppressor gene BRCA1 without affecting the cell-cycle control protein p21Waf/Cip1. Some POCs therefore have the potential to affect breast cancer risk. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|