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ESR1 Gene Expression in Oncology and Metabolic Diseases Using the ASCENTATM System ,,, Target Validation and Identification of Novel Disease Indications

ARM1 (coactivator-associated arginine methyltransferase) methylates many proteins that modulate transcriptional regulation and is a coactivator of gene transcription for ESR1. Pelp1 (Proline-, glutamic acid-, leucine-rich protein 1) is a scaffold protein that may mediate the rapid cellular proliferation response transduced by ESR1 in response to estrogen binding. These pathways can be used as gene sets in the ASCENTA System to explore how they are regulated in the aforementioned oncology and metabolic disease therapeutic areas that display ESR1 regulation. These two pathway reports may provide new insight into the disease-specific gene expression modulation of ESR1 and related gene targets for followup studies.

These findings, combined with the pathway analysis for ESR1 seen in Figure 5, provide a global picture of ESR1 function in both normal biology and in human disease. This gene is clearly involved in cellular proliferation, transcriptional activation, and growth in response to steroid hormones. Regulation of this gene or other members of the cellular machinery with which it interacts can lead to abnormal growth conditions such as cancer. A broader understanding of the biological networks related to ESR1 function is easily obtained using the ASCENTA System. This global perspective may further facilitate the identification of additional pathways or gene families that could serve as alternative targets for novel disease therapeutics.

Conclusions

This Application Note demonstrates how the ASCENTA System can be used to quickly and easily examine expression levels of target genes, such as ESR1, across pre-selected tissue sample sets to determine where they are differentially regulated in hundreds of disease morphologies. In addition, the advanced analysis features of the ASCENTA System, such as pathway analysis, clearly demonstrate how a gl
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