A novel molecular assay to discriminate transcriptional effects caused by xenoestrogens.

Mol Cell Endocrinol

Institute for Hormone and Fertility Research, University of Hamburg, 20246 Hamburg, Germany.

Published: September 2007

AI Article Synopsis

  • The definition of estrogen has become complex due to its various actions through different receptors and signaling pathways, complicating how substances like xenoestrogens are categorized.
  • A novel transfection system using MBA-MD231 and MCF-7 breast cancer cells allows for the examination of both classical and non-classical estrogen actions by altering nuclear receptor types and promoter-reporter constructs.
  • This assay matrix has been applied to investigate various phytoestrogens and xenobiotics, shedding light on their mechanisms of action in breast cancer cells.

Article Abstract

A phenotypic definition of the term estrogen has become increasingly problematic due to the multiple modes of estrogen action which can now be defined by differing nuclear and membrane receptors for the classic ligand, 17beta-estradiol, and by the multiple signalling pathways that are consequently addressed. This has led to the term xenoestrogen being largely determined by whatever assay system is used for its definition. Here we describe a novel and simple matrix for a transfection system using MBA-MD231 and MCF-7 breast cancer cells as hosts. This matrix is able to vary the type of nuclear estrogen receptor used, and by varying the promoter-reporter construct between one using a classic estrogen response element (ERE) enhancer, and one using an enhancer element derived from the bovine oxytocin gene promoter binding an orphan nuclear receptor, direct classical effects can be neatly discriminated from non-classical and non-genomic actions of test substances. This assay matrix has been used to examine a selection of phytoestrogens and xenobiotics, thereby providing new information on the mechanism of action of some of these substances in breast cancer cells.

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http://dx.doi.org/10.1016/j.mce.2007.06.008DOI Listing

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