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Majority of breast and ovarian cancer treatment modalities are based on endocrine therapies like antiestrogens which are dependent on the hormone receptor status of tumours. Although BRCA1 is a major regulator of Estrogen Receptor (ER-α), BRCA1 mutations are largely limited to hereditary cases. Here, we show the role of NBR2 (neighbour of BRCA1) in regulating ER-α. We demonstrate a positive correlation between NBR2 & ESR1 in TCGA datasets. Further, the study revealed that shRNA-mediated knockdown of NBR2 led to the downregulation of ER-α in breast cancer cells, MCF7. Finally, the downregulation of ER-α in NBR2 knockdown xenograft tumours (in female NSG mice), which showed higher invasive properties than wild type tumours was demonstrated. Thus, we concluded that in ER-α negative tumours with NBR2 deficiency, biguanides such as metformin and phenformin, which are reported to have a better efficacy under NBR2 deficient conditions, could serve as more suitable alternatives to antiestrogens.