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• W2892330346 abstract "// Moses Koobotse 1, 2 , Jeff Holly 1 and Claire Perks 1 1 IGFs and Metabolic Endocrinology Group, Translational Health Sciences, University of Bristol, Bristol, UK 2 Faculty of Health Sciences, School of Allied Health Professions, University of Botswana, Gaborone, Botswana Correspondence to: Claire Perks, email: claire.m.perks@bristol.ac.uk Keywords: BRCA1; IGF-I; cancer; p-ACCA; non-genomic Received: May 09, 2018      Accepted: August 04, 2018      Published: September 11, 2018 ABSTRACT Within populations carrying the same genetic predisposition, the penetrance of BRCA1 mutations has increased over time. Although linked to changes in lifestyle factors associated with energy metabolism, these observations cannot be explained by the established role of BRCA1 in DNA repair alone. We manipulated BRCA1 expression using tetracycline in the UBR60-bcl2 cell line (which has an inducible, tetracycline-regulated BRCA1 expression) and siRNA in oestrogen receptor(ER)-positive MCF7 and T47D breast cancer cells. Cellular responses to BRCA1 silencing and IGF-I actions were investigated using western blotting, 3-H Thymidine incorporation assay, cell fractionation and co-immunoprecipitation. We demonstrated that the loss of BRCA1 resulted in downregulation of a phosphorylated and inactive form of acetyl CoA Carboxylase-α (ACCA), with a concomitant increase in fatty acid synthase (FASN) abundance. BRCA1 was predominantly cytoplasmic in ER-positive breast cancer cells, compatible with the observation that BRCA1 physically associates with phosphorylated ACCA, which is a cytoplasmic protein. We also found that IGF-I induced de-phosphorylation of ACCA by reducing the interaction between BRCA1 and phosphorylated ACCA. BRCA1 deficiency enhanced the non-genomic effects of IGF-I, as well as the proliferative responses of cells to IGF-I. We characterized a novel, non-genomic role for BRCA1 in restraining metabolic activity and IGF-I anabolic actions." @default.
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• W2892330346 date "2018-09-11" @default.
• W2892330346 modified "2023-09-26" @default.
• W2892330346 title "Elucidating the novel BRCA1 function as a non-genomic metabolic restraint in ER-positive breast cancer cell lines" @default.
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• W2892330346 doi "https://doi.org/10.18632/oncotarget.26093" @default.
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