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

: Oncology, Inflammation, Cardiovascular Disease, Central Nervous System Disorders and Metabolic Diseases. This information can be used to examine the specificity and scope of expression regulation to validate genes as priority drug targets for treatment of a specific disease or to uncover additional disease indications that may broaden the importance and applicability of gene targets as drug candidates.

The Diff/X report in Figure 2 shows that ESR1 was elevated (positive fold change) in ERpositive (ER+) infiltrating ductal carcinoma of the breast (the most common histologic variant), relative to normal and fibrocystic breast tissue and to ER-negative (ER-) carcinoma of the same histologic type. These data are in agreement with what has been reported in the literature (2).

Additional results in oncology revealed a significant decrease in ESR1 expression in a variety of conditions leading to cirrhosis of the liver and more marked downregulation in hepatocellular carcinoma (Figure 3). The presence of cirrhosis (a non-malignant condition) is known to significantly increase the risk of developing hepatocellular carcinoma. This correlation of down-regulated ESR1 expression with liver cirrhosis and hepatocellular carcinoma is an interesting finding, as ESR1 has recently been shown to be down regulated in hepatocellular carcinomas (3), but has not been reported in liver cirrhosis.

The ASCENTA System also identified additional novel therapeutic indications for ESR1 (Figure 4) in metabolic diseases. ESR1 expression was down-regulated in morphologically normal liver tissue from diabetic patients as compared to tissue from nondiabetic patients; and in skeletal muscle from obese and/or diabetic patients as compared to non-obese and/or non-diabetic patients. It is known that ESR1 knock-out mice show adipocyte hyperplasia and hypertrophy (i.e. obesity), as well as insulin resistance (a feature of diabetes) (4). These mo
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