Xenoestrogens and the induction of proliferative effects in breast cancer cells via direct activation of oestrogen receptor α
- 1 February 2004
- journal article
- research article
- Published by Taylor & Francis in Food Additives & Contaminants
- Vol. 21 (2), 134-144
- https://doi.org/10.1080/02652030310001641177
Abstract
Environmental contamination with a variety of industrial products has been associated with developmental and reproductive abnormalities in wildlife species. Increasing evidence has suggested that bisphenol A (BPA) and 4-nonylphenol (NPH), two major endocrine-disrupting chemicals, might be responsible for adverse effects on humans as a consequence of ubiquitous use together with potential oestrogen-like activity. To provide insight into the oestrogen-like nature of BPA and NPH, their ability to activate a reporter gene construct via an oestrogen response element in the hormone-dependent breast cancer cell lines MCF7 and T47D was ascertained. Both compounds transactivated the endogenous oestrogen receptor (ER) α in a direct fashion since the anti-oestrogen 4-hydroxytamoxifen abolished the response. In addition, using steroid-receptor-negative HeLa cells engineered to express ERα and ERβ and the hormone-binding domains of both ERα and ERβ, BPA and NPH confirmed the direct transcriptional activity. Interestingly these properties were supported in MCF7 cells by the ability to autoregulate ERα expression as well as to induce its nuclear compartmentalization. We therefore evaluated by reverse transcriptase polymerase chain reaction the expression of oestrogen-controlled genes such as cathepsin D and TFF1 (formerly pS2), which were increased by both chemicals tested. The agonistic effects exhibited in all assays performed prompted the evaluation of a more complex biological response such as the proliferation of MCF7 and T47D cells. The same concentration of xenoestrogens eliciting substantial transcriptional activity significantly stimulated the proliferation of both breast cancer cell lines, although with a reduced effectiveness with respect to the natural hormone 17β-oestradiol. The results indicate that the biological action of environmental oestrogen such as BPA and NPH should be taken into account for the potential impact on human disease-like hormone-dependent breast cancer. However, further studies are needed to clarify their bioavailability and metabolism as well as whether compound mixtures could produce noticeable effects by synergistic activity.Keywords
This publication has 56 references indexed in Scilit:
- Deuterium Labelled Nonylphenols in anin-vitroModel of Percutaneous Absorption of Environmental XenoestrogensIsotopes in Environmental and Health Studies, 2000
- Hormone-Dependent Coactivator Binding to a Hydrophobic Cleft on Nuclear ReceptorsScience, 1998
- Molecular basis of agonism and antagonism in the oestrogen receptorNature, 1997
- Editorial: Estrogens from Plastic--Are We Being Exposed?Endocrinology, 1997
- Evaluation of Chemicals with Endocrine Modulating Activity in a Yeast-Based Steroid Hormone Receptor Gene Transcription AssayToxicology and Applied Pharmacology, 1997
- Endocrine disruptors and reproductive development: a weight-of-evidence overviewJournal of Endocrinology, 1997
- Transcriptional regulation by steroid hormonesSteroids, 1996
- Xenoestrogens Released from Lacquer Coatings in Food CansEnvironmental Health Perspectives, 1995
- Evidence of prenatal influences on breast cancer riskThe Lancet, 1992
- Evidence for decreasing quality of semen during past 50 years.BMJ, 1992