scholarly journals RANK is an independent biomarker of poor prognosis in estrogen receptor-negative breast cancer and a therapeutic target in patient-derived xenografts

2021 ◽  
Author(s):  
Marina Ciscar ◽  
Eva M Trinidad ◽  
Hector Perez-Montoyo ◽  
Mansour Alsaleem ◽  
Maria J Jimenez-Santos ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Poor Prognosis ◽  
Immune Surveillance ◽  
Therapeutic Benefit ◽  
Biological Processes ◽  
Rankl Expression ◽  
Functional Studies ◽  
Gene Expression Analyses ◽  
Rank Signaling ◽  
Estrogen Receptor Negative

Despite strong preclinical data, the therapeutic benefit of the RANKL inhibitor denosumab in BC patients, beyond its bone-related effects, is unclear. Here, we investigated the prognostic value of RANK expression and its functionality in human BC. We analyzed RANK and RANKL expression in more than 1500 BC cases (777 being estrogen receptor-negative (ER-)) from four independent cohorts. We confirmed that RANK was more frequently expressed in ER- tumors, but it is also found in a subset of ER+ tumors. In ER- BC, RANK expression was independently associated with poor outcome, especially in postmenopausal patients and those who received adjuvant chemotherapy. Gene expression analyses unraveled distinct biology associated with RANK in relation to ER expression and menopause, and enhanced RANK activation in ER- postmenopausal tumors. Functional studies and transcriptomic analyses in ER- RANK+ patients-derived orthoxenografts demonstrated that activation of RANK signaling pathway promotes tumor cell proliferation and stemness, and regulates multiple biological processes including tumor immune surveillance and metabolism. Our results demonstrate that RANK expression is an independent poor prognosis biomarker in postmenopausal ER- BC patients and support the rational of using RANK pathway inhibitors in combination with chemotherapy in ER- BC.

scholarly journals Decreased BECN1 mRNA Expression in Human Breast Cancer is Associated With Estrogen Receptor-Negative Subtypes and Poor Prognosis

EBioMedicine ◽  
2015 ◽  
Vol 2 (3) ◽  
pp. 255-263 ◽  
Author(s):  
Hao Tang ◽  
Salwa Sebti ◽  
Rossella Titone ◽  
Yunyun Zhou ◽  
Ciro Isidoro ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Mrna Expression ◽  
Human Breast Cancer ◽  
Poor Prognosis ◽  
Human Breast ◽  
Estrogen Receptor Negative

Increased wound-response revealed by proteomics of estrogen receptor-negative breast cancers

2008 ◽  
Vol 68 (S 01) ◽  
Author(s):  
H Neubauer ◽  
K Sotlar ◽  
D Wallwiener ◽  
MA Cahill ◽  
E Solomayer ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Wound Response ◽  
Breast Cancers ◽  
Estrogen Receptor Negative

scholarly journals Systematic integrated analyses of methylomic and transcriptomic impacts of early combined botanicals on estrogen receptor-negative mammary cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Itika Arora ◽  
Yuanyuan Li ◽  
Manvi Sharma ◽  
Michael R. Crowley ◽  
David K. Crossman ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Early Life ◽  
Mammary Cancer ◽  
Epigenetic Modifications ◽  
Green Tea Polyphenols ◽  
Cruciferous Vegetable ◽  
Exciting Potential ◽  
Genomic Scale ◽  
Functional Analyses ◽  
Estrogen Receptor Negative

AbstractDietary botanicals such as the cruciferous vegetable broccoli sprouts (BSp) as well as green tea polyphenols (GTPs) have shown exciting potential in preventing or delaying breast cancer (BC). However, little is known about their impact on epigenomic aberrations that are centrally involved in the initiation and progression of estrogen receptor-negative [ER(−)] BC. We have investigated the efficacy of combined BSp and GTPs diets on mammary tumor inhibition in transgenic Her2/neu mice that were administered the diets from prepubescence until adulthood. Herein, we present an integrated DNA methylome and transcriptome analyses for defining the early-life epigenetic impacts of combined BSp and GTPs on mammary tumors and our results indicate that a combinatorial administration of BSp and GTPs have a stronger impact at both transcriptome and methylome levels in comparison to BSp or GTPs administered alone. We also demonstrated a streamlined approach by performing an extensive preprocessing, quality assessment and downstream analyses on the genomic dataset. Our identification of differentially methylated regions in response to dietary botanicals administered during early-life will allow us to identify key genes and facilitate implementation of the subsequent downstream functional analyses on a genomic scale and various epigenetic modifications that are crucial in preventing ER(−) mammary cancer. Furthermore, our realtime PCR results were also found to be consistent with our genome-wide analysis results. These results could be exploited as a comprehensive resource for understanding understudied genes and their associated epigenetic modifications in response to these dietary botanicals.

scholarly journals Hypoxia Transcriptomic Modifications Induced by Proton Irradiation in U87 Glioblastoma Multiforme Cell Line

2021 ◽  
Vol 11 (4) ◽  
pp. 308
Author(s):  
Valentina Bravatà ◽  
Walter Tinganelli ◽  
Francesco P. Cammarata ◽  
Luigi Minafra ◽  
Marco Calvaruso ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Cell Line ◽  
Acute Hypoxia ◽  
Hypoxic Condition ◽  
Biological Processes ◽  
Microarray Gene Expression ◽  
Hypoxic Conditions ◽  
Gene Expression Analyses ◽  
Shed Light ◽  
New Strategies

In Glioblastoma Multiforme (GBM), hypoxia is associated with radioresistance and poor prognosis. Since standard GBM treatments are not always effective, new strategies are needed to overcome resistance to therapeutic treatments, including radiotherapy (RT). Our study aims to shed light on the biomarker network involved in a hypoxic (0.2% oxygen) GBM cell line that is radioresistant after proton therapy (PT). For cultivating cells in acute hypoxia, GSI’s hypoxic chambers were used. Cells were irradiated in the middle of a spread-out Bragg peak with increasing PT doses to verify the greater radioresistance in hypoxic conditions. Whole-genome cDNA microarray gene expression analyses were performed for samples treated with 2 and 10 Gy to highlight biological processes activated in GBM following PT in the hypoxic condition. We describe cell survival response and significant deregulated pathways responsible for the cell death/survival balance and gene signatures linked to the PT/hypoxia configurations assayed. Highlighting the molecular pathways involved in GBM resistance following hypoxia and ionizing radiation (IR), this work could suggest new molecular targets, allowing the development of targeted drugs to be suggested in association with PT.

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