AKT Alters Genome-Wide Estrogen Receptor α Binding and Impacts Estrogen Signaling in Breast Cancer

• DOI: 10.1128/mcb.00799-08
• Publication Date: 2008-10-07T00:44:49Z
• Authors: Poornima Bhat-Nak...; Guohua Wang; Hitesh Appaiah; Nikhil Luktuke; Jason S. Carroll; Tim R. Geistlinger; Myles Brown; Sunil Badve; Yunlong Liu; Harikrishna Naksh...
• Keywords: Estrogen receptor alpha; Estrogen receptor beta

Estrogen regulates several biological processes through estrogen receptor alpha (ERalpha) and ERbeta. ERalpha-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 ERalpha binding in MCF-7 breast cancer cells. Parental AKT-overexpressing cells displayed 4,349 4,359 sites, respectively, with approximately 60% overlap. both cell types, 40% estrogen-regulated genes associate sites; a similar percentage are differentially expressed two types. Based pathway analysis, these linked to transforming growth factor beta (TGF-beta), NF-kappaB, E2F pathways. Consistent this, types responded differently TGF-beta treatment: parental cells, but not required overcome inhibition. Combining DNA-binding pattern gene expression data from primary tumors revealed specific effects that define prognostic subgroups tamoxifen sensitivity ERalpha-positive cancer. These results suggest unique role modulating cancers highlights how can change landscape transcription genome.