%0 Journal Article
%T Argonaute 2 Expression Correlates with a Luminal B Breast Cancer Subtype and Induces Estrogen Receptor Alpha Isoform Variation
%A Adrienne K. Conger
%A Brian G. Rowan
%A Bridgette M. Collins-Burow
%A Elizabeth C. Martin
%A Hope E. Burks
%A Jacqueline La
%A Kenneth P. Nephew
%A Lyndsay V. Rhodes
%A Matthew E. Burow
%A Muralidharan Anbalagan
%A Thomas J. Yan
%A Van T. Hoang
%J Archive of "Non-Coding RNA".
%D 2016
%R 10.3390/ncrna2030008
%X Estrogen receptor alpha (ER¦Á) signaling pathways are frequently disrupted in breast cancer and contribute to disease progression. ER¦Á signaling is multifaceted and many ER¦Á regulators have been identified including transcription factors and growth factor pathways. More recently, microRNAs (miRNAs) are shown to deregulate ER¦Á activity in breast carcinomas, with alterations in both ER¦Á and miRNA expression correlating to cancer progression. In this study, we show that a high expression of Argonaute 2 (AGO2), a translation regulatory protein and mediator of miRNA function, correlates with the luminal B breast cancer subtype. We further demonstrate that a high expression of AGO2 in ER¦Á+ tumors correlates with a poor clinical outcome. MCF-7 breast cancer cells overexpressing AGO2 (MCF7-AGO2) altered ER¦Á downstream signaling and selective ER¦Á variant expression. Enhanced ER¦Á-36, a 36 kDa ER¦Á isoform, protein and gene expression was observed in vitro. Through quantitative polymerase chain reaction (qPCR), we demonstrate decreased basal expression of the full-length ER¦Á and progesterone receptor genes, in addition to loss of estrogen stimulated gene expression in vitro. Despite the loss, MCF-7-AGO2 cells demonstrated increased estrogen stimulated tumorigenesis in vivo. Together with our clinical findings on AGO2 expression and the luminal B subtype, we suggest that AGO2 is a regulator of altered ER¦Á signaling in breast tumors
%K AGO2
%K estrogen receptor
%K isoform
%K luminal B
%K miRNA
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5831908/