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Defective Signalling of the BRCA1 Neighbouring gene, NBR2, leads to ER-? Negative tumours in breast cancer xenograft mouse models
Dipyaman Patra, Geetu Rose Varghese, Krithiga Kuppusamy, Neethu Krishnan and Priya Srinivas
doi: https://doi.org/10.51966/jvas.2022.53.4.772-776
Journal of Veterinary and Animal Sciences.2022.53(4):772-776.
Author Details
Dipyaman Patra : Ph.D. Scholar, Cancer Research Program-6, Rajiv Gandhi Centre for Biotechnology, Thycaud PO, Thiruvananthapuram 695 014, Kerala, India. Research centre, University of Kerala, Thiruvananthapuram, Kerala, India
Geetu Rose Varghese : Ph.D. Scholar, Cancer Research Program-6, Rajiv Gandhi Centre for Biotechnology, Thycaud PO, Thiruvananthapuram 695 014, Kerala, India. Research centre, University of Kerala, Thiruvananthapuram, Kerala, India
Krithiga Kuppusamy : Assistant Professor, Bioscience Research and Training Centre, Thonnakkal
Neethu Krishnan : Ph.D. Scholar, Cancer Research Program-6, Rajiv Gandhi Centre for Biotechnology, Thycaud PO, Thiruvananthapuram 695 014, Kerala, India. Research centre, University of Kerala, Thiruvananthapuram, Kerala, India
Priya Srinivas : Scientist-G
Article History
Received: 19.10.2022, Accepted: .2022, Published online: 31.12.2022
Corresponding author: Priya Srinivas
e-mail : priyasrinivas@rgcb.res.in
Citation: J. Vet. Anim. Sci. 53(4): 772-776
DOI: https://doi.org/10.51966/jvas.2022.53.4.772-776
Abstract
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.
Keywords: Breast cancer, ER-α, NBR2
