Genome-wide activity of unliganded estrogen receptor-α in breast cancer cells

Caizzi, Livia; Ferrero, Giulio; Cutrupi, Santina; Cordero, Francesca; Ballaré, Cecilia; Miano, Valentina; Reineri, Stefania; Ricci, Luisa; Friard, Olivier; Testori, Alessandro; Corà, Davide; Caselle, Michele; Croce, Luciano Di; Bortoli, Michele De

doi:10.1073/pnas.1315445111

Cited by 75 publications

(108 citation statements)

References 39 publications

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“…3). A recent study demonstrated a role of AP2g in chromatin binding of unliganded ERa and unliganded ERa-regulating AP2g expression (47). AP2g is also essential for ERa-mediated long-range chromatin interaction (48).…”

Section: Discussionmentioning

confidence: 99%

Molecular Insights of Pathways Resulting from Two Common PIK3CA Mutations in Breast Cancer

et al. 2016

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The PI3K pathway is activated in approximately 70% of breast cancers. PIK3CA gene mutations or amplifications that affect the PI3K p110a subunit account for activation of this pathway in 20% to 40% of cases, particularly in estrogen receptor alpha (ERa)-positive breast cancers. AKT family of kinases, AKT1-3, are the downstream targets of PI3K and these kinases activate ERa. Although several inhibitors of PI3K have been developed, none has proven effective in the clinic, partly due to an incomplete understanding of the selective routing of PI3K signaling to specific AKT isoforms. Accordingly, we investigated in this study the contribution of specific AKT isoforms in connecting PI3K activation to ERa signaling, and we also assessed the utility of using the components of PI3K-AKT isoform-ERa signaling axis as predictive biomarkers of response to PI3K inhibitors. Using a variety of physiologically relevant model systems with defined natural or knock-in PIK3CA mutations and/or PI3K hyperactivation, we show that PIK3CA-E545K mutations (found in $20% of PIK3CA-mutant breast cancers), but not PIK3CA-H1047R mutations (found in 55% of PIK3CA-mutant breast cancers), preferentially activate AKT1. Our findings argue that AKT1 signaling is needed to respond to estrogen and PI3K inhibitors in breast cancer cells with PIK3CA-E545K mutation, but not in breast cancer cells with other PIK3CA mutations. This study offers evidence that personalizing treatment of ER-positive breast cancers to PI3K inhibitor therapy may benefit from an analysis of PIK3CA-E545K-AKT1-estrogen signaling pathways. Cancer Res; 76(13); 3989-4001. Ó2016 AACR.

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Section: Discussionmentioning

confidence: 99%

Molecular Insights of Pathways Resulting from Two Common PIK3CA Mutations in Breast Cancer

et al. 2016

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“…In particular, genes possessing preferential binding sites for SRC3 have predictive value for clinical outcome [79] . Moreover, in MCF7 cells, unliganded ERα binding to many sites in the chromatin is considered to be involved in maintenance of hormone-dependent breast cancer cells [80] .…”

Section: Identification Of Estrogen-responsive Genes Using Highthrougmentioning

confidence: 99%

Identification of estrogen-responsive genes based on the DNA binding properties of estrogen receptors using high-throughput sequencing technology

2014

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Estrogens are important endocrine hormones that control physiological functions in reproductive organs, and play a pivotal role in the generation and progression of breast cancer. Therapeutic drugs including anti-estrogen and aromatase inhibitors are used to treat patients with breast cancer. The estrogen receptors, ERα and ERβ, function as hormone-dependent transcription factors that directly regulate the expression of their target genes. Therefore, a better understanding of the function and regulation of estrogen-responsive genes provides insight into the gene regulation network associated with breast cancer. Recent technological developments in highthroughput sequencing have enabled the genome-wide identification of estrogen-responsive genes. Further elucidating the estrogen gene cascade is critical for advancements in the diagnosis and treatment of breast cancer.

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“…It is also reported that CD200 could be a new prognostic factor in acute myeloid leukaemia (21). ESR1, a ligand-activated transcription factor, involves in pathological processes of breast (22)(23)(24)(25), prostate (26) and non-small cell lung cancer (27).…”

Section: Discussionmentioning

confidence: 99%

Gene expression profile for predicting survival of patients with meningioma

Chen

Xiang

Zhou

et al. 2014

International Journal of Oncology

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Abstract. Current staging methods are inadequate for predicting the overall survival of meningioma. DNA microarray technologies improve the understanding of tumour progression. We analysed genome wide expression profiles of 119 meningioma samples from two previous published DNA microarray studies. The Cox proportional hazards regression models were applied to identify overall survival related gene signature. A total of 449 genes (109 upregulated and 340 downregulated) were identified as differentially expressed in meningioma. Among these differentially expressed genes, 37 genes were identified to be related to meningioma overall survival. Our 37-gene signature is closely associated with overall survival among patients with meningioma. This gene expression profile could provide an optimization of the clinical management and development of new therapeutic strategies for meningioma.

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Genome-wide activity of unliganded estrogen receptor-α in breast cancer cells

Cited by 75 publications

References 39 publications

Molecular Insights of Pathways Resulting from Two Common PIK3CA Mutations in Breast Cancer

Molecular Insights of Pathways Resulting from Two Common PIK3CA Mutations in Breast Cancer

Identification of estrogen-responsive genes based on the DNA binding properties of estrogen receptors using high-throughput sequencing technology

Gene expression profile for predicting survival of patients with meningioma

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