Interpretation of the in Vitro Proliferation Response of MCF-7 Cells to Potential Oestrogens and Non-Oestrogenic Substances

Abstract

Chemicals may interact with the oestrogen receptor (ER) in mammalian cells and thereby exhibit oestrogenic activity which may result in effects on development and reproduction in both wildlife and humans. It has been suggested that in vitro assays provide the best way forward for investigating the oestrogenic potential of large numbers of chemicals. We compared the effects of a series of chemicals in an MCF-7 cell proliferation assay with results from similar assays reported in the literature in order to investigate the practical use of such assays. Alkylphenols and benzylbutylphthalate were found to cause proliferation of MCF-7 cells, which could be antagonized by tamoxifen. However, all the substances tested, including ethanol, progesterone and epidermal growth factor, were found to have some effect on cell proliferation, suggesting that cell proliferation may result from mechanisms other than via the ER. This is in contrast to some reports that MCF-7 cells only respond to oestrogens and highlights MCF-7 cell strain differences. Such differences and other reports in the literature of the effects of growth modulators on MCF-7 cells indicate that interpretation of results from MCF-7 cell proliferation assays needs to be considered carefully. Comparison between the results of in vitro assays and appropriate in vivo assays is also required in order to evaluate the significance of in vitro oestrogenicity assay results and an understanding of the mechanisms responsible for the biological effects is necessary.