( sue sample sets that display the highes...)ESR1 Gene Expression in Oncology and Metabolic Diseases Using the ASCENTATM System ,,, Target Validation and Identification of Novel Disease Indications

sue sample sets that display the highest expression levels of ESR1. Female reproductive tissues (uterus, fallopian tube, breast and ovary) have the highest degree of ESR1 expression, followed by liver, artery, prostate, skeletal muscle, skin and adipose tissues. ESR1 gene expression was notably absent, or below the limit of detection, in cells and tissues comprising the immune and central nervous systems (data not shown).

Knowledge of gene target expression levels in human cell lines is often used as a criterion to select specific cell types for further in vitro validation of genes as drug targets. For example, cell lines that highly express a gene target can be used for RNAi studies to determine the biological effect of "knock-down", whereas cell lines that do not express specific gene targets can be used for gene transfection studies to determine the impact of increased expression. We examined ESR1 gene expression levels in a panel of 60 commonly used human-derived cell lines (referred to as the "NCI-60 panel"), many of which are directly applicable to oncology studies. The ESR1 e-Northern report from the NCI-60 panel (data not shown) demonstrated that ESR1 was highly expressed in the MCF7 and T47D breast cancer cell lines and to a lesser yet significant level in the SK-OV-3 ovarian cancer cell line. ESR1 expression was not detected in several prostate, lung and colonderived cell lines.

The specificity and extent of expression regulation of a gene target with respect to human disease is another important metric that is used to select and prioritize genes as candidates for further development in drug discovery R&D pipelines. The ASCENTA System provides readily available gene expression regulation information in the form of a Diff/X report, which lists statistically significant regulation events in hundreds of human diseases with respect to control or normal morphologies, all contained within five major therapeutic areas
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