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Interactions between the estrogen receptor, its cofactors and micrornas in breast cancer
McCafferty, Marc P. J.; McNeill, Roisin E.; Miller, Nicola; Kerin, Michael J.
The activity of selective estrogen receptor modulators (SERMs) is not fully explained by an estrogen receptor (ER) switch model that simply turns estrogen activity on or off. A better understanding of the mechanisms involved in estrogen signaling and the development of drug resistance could help stratify patients into more coherent treatment groups and identify novel therapeutic candidates. This review describes how interactions between two novel factors known to influence estrogenic activity: nuclear receptor cofactors-protein partners which modulate estrogen action, and microRNAs-a class of recently discovered regulatory elements, may impact hormone-sensitive breast cancer. The role of nuclear receptor cofactors in estrogen signaling and the associations between ER cofactors and breast cancer are described. We outline the activity of microRNAs (miRNAs) and their associations with breast cancer and detail recent evidence of interactions between the ER and its cofactors and miRNA and provide an overview of the emerging field of miRNA-based therapeutics. We propose that previously unrecognised interactions between these two species of regulatory molecules may underlie at least some of the heterogeneity of breast cancer in terms of its clinical course and response to treatment. The exploitation of such associations will have important implications for drug development.
Keyword(s): breast cancer; estrogen receptors; estrogen receptor cofactors; endocrine resistance; micrornas; nuclear hormone-receptors; tumor-suppressor gene; tamoxifen resistance; transcriptional activation; binding coactivator; molecular portraits; signaling pathways; randomized-trials; rnai therapeutics; ovarian-cancer
Publication Date:
2018
Type: Journal article
Peer-Reviewed: Unknown
Institution: NUI Galway
Publisher(s): Springer Nature
First Indexed: 2019-03-23 06:25:30 Last Updated: 2019-03-23 06:25:30