Bhat-Nakshatri, PoornimaWang, GuohuaAppaiah, HiteshLuktuke, NikhilCarroll, Jason S.Geistlinger, Tim R.Brown, MylesBadve, SunilLiu, YunlongNakshatri, Harikrishna2019-04-012019-04-012008-12Bhat-Nakshatri, P., Wang, G., Appaiah, H., Luktuke, N., Carroll, J. S., Geistlinger, T. R., … Nakshatri, H. (2008). AKT Alters Genome-Wide Estrogen Receptor α Binding and Impacts Estrogen Signaling in Breast Cancer. Molecular and Cellular Biology, 28(24), 7487–7503. https://doi.org/10.1128/MCB.00799-080270-7306https://hdl.handle.net/1805/18751[LINK]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2593438/[/LINK]Estrogen regulates several biological processes through estrogen receptor α (ERα) and ERβ. ERα-estrogen signaling is additionally controlled by extracellular signal activated kinases such as AKT. In this study, we analyzed the effect of AKT on genome-wide ERα binding in MCF-7 breast cancer cells. Parental and AKT-overexpressing cells displayed 4,349 and 4,359 ERα binding sites, respectively, with ∼60% overlap. In both cell types, ∼40% of estrogen-regulated genes associate with ERα binding sites; a similar percentage of estrogen-regulated genes are differentially expressed in two cell types. Based on pathway analysis, these differentially estrogen-regulated genes are linked to transforming growth factor β (TGF-β), NF-κB, and E2F pathways. Consistent with this, the two cell types responded differently to TGF-β treatment: parental cells, but not AKT-overexpressing cells, required estrogen to overcome growth inhibition. Combining the ERα DNA-binding pattern with gene expression data from primary tumors revealed specific effects of AKT on ERα binding and estrogen-regulated expression of genes that define prognostic subgroups and tamoxifen sensitivity of ERα-positive breast cancer. These results suggest a unique role of AKT in modulating estrogen signaling in ERα-positive breast cancers and highlights how extracellular signal activated kinases can change the landscape of transcription factor binding to the genome.en-USEstrogen ReceptorBreast CancerAKTArticle10.1128/MCB.00799-08