Breast cell-based assays

Ishikawa cell stimulation were then tested in ovariectomized rats for the ability to protect against loss of bone mineral density. It was found that GW5638 had antagonist properties on the uterus and agonist activities on bone and the cardiovascular system [59]. In further experiments it was shown that the biological properties of GW5638 derive from triggering a structural conformation of ER different from the conformations imposed by other SERMs [60]. Recently, several novel SERMs (e.g. bazedoxifene, lasofoxifene) have been identified with a combination of cellular screens, primarily uterine- and breast cell-based assays [61-63] (Scheme 1.4). 

The estrogenic and antiestrogenic activities of several PBDE congeners and three hydroxylated PBDEs were tested in vitro using human breast cell line assays based on estrogen receptor (ER)-dependent luciferase reporter gene expression (Mccrts et al. 2001). The hydroxylated PBDEs,... 

Figure 4 Cytotoxicity of HER2-directed liposomal APE in HER2-overexpressing BT474 human breast carcinoma cells. Cells were plated at a density of 5000 ceUs/well and incubated for four hours with varying concentrations of unencapsulated ( ), liposomal (O), or antiHER2 (E5)-immunoliposomal (A) Cells were assayed for viability using a standard tetrazolium-based assay three days later. Abbreviation. APE, 6-(3-aminopropyl)ellipticine.

Yeast reporter gene assays and MCF-7 cell-based proliferation assays (E-screen) are particularly popular. The E-screen, in which proliferation of human breast cancer cells (MCF-7) is measured as a response to estrogen, has also been used to determine the estrogenicity of sewage effluent and surface water (Kdrner et al., 2001). 

Cell proliferation assays. The most commonly known is the E-Screen (first described by Soto et al., 1992), which is based on the proliferation of the cells of the MCF-7 human breast cancer cell line (Komer et al., 1999). 

Ramamoorthy K, Wang F, Chen I-C, et al. 1997. Estrogenic activity of a dieldrin/toxaphene mixture in the mouse uterus, MCF-7 human breast cancer cells, and yeast-based estrogen receptor assays No apparent synergism. Endocrinology 138(4) 1520-1527. 

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