scholarly journals Xanthohumol suppresses oestrogen-signalling in breast cancer through the inhibition of BIG3-PHB2 interactions

2014 ◽  
Vol 4 (1) ◽  
Author(s):  
Tetsuro Yoshimaru ◽  
Masato Komatsu ◽  
Etsu Tashiro ◽  
Masaya Imoto ◽  
Hiroyuki Osada ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Oestrogen Signalling

scholarly journals Molecular basis of distinct oestrogen responses in endometrial and breast cancer

2019 ◽  
Vol 26 (1) ◽  
pp. 31-46 ◽  
Author(s):  
Eva Baxter ◽  
Karolina Windloch ◽  
Greg Kelly ◽  
Jason S Lee ◽  
Frank Gannon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Transcriptional Activation ◽  
The Cancer Genome Atlas ◽  
Breast Cancers ◽  
Oestrogen Receptor Alpha ◽  
Limited Success ◽  
Cancer Genome Atlas ◽  
Using Data ◽  
Oestrogen Signalling

Up to 80% of endometrial and breast cancers express oestrogen receptor alpha (ERα). Unlike breast cancer, anti-oestrogen therapy has had limited success in endometrial cancer, raising the possibility that oestrogen has different effects in both cancers. We investigated the role of oestrogen in endometrial and breast cancers using data from The Cancer Genome Atlas (TCGA) in conjunction with cell line studies. Using phosphorylation of ERα (ERα-pSer118) as a marker of transcriptional activation of ERα in TCGA datasets, we found that genes associated with ERα-pSer118 were predominantly unique between tumour types and have distinct regulators. We present data on the alternative and novel roles played by SMAD3, CREB-pSer133 and particularly XBP1 in oestrogen signalling in endometrial and breast cancer.

scholarly journals Novel flavonoids as anti-cancer agents: mechanisms of action and promise for their potential application in breast cancer

2014 ◽  
Vol 42 (4) ◽  
pp. 1017-1023 ◽  
Author(s):  
Carlos Martinez-Perez ◽  
Carol Ward ◽  
Graeme Cook ◽  
Peter Mullen ◽  
Donald McPhail ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Potential Application ◽  
Great Promise ◽  
Effective Mechanism ◽  
Cycle Arrest ◽  
Antioxidant Agents ◽  
Wide Range ◽  
Anti Cancer ◽  
Oestrogen Signalling ◽  
Anti Tumour Effect

Flavonoids are a large group of ubiquitous polyphenolic secondary metabolites in plants with a wide range of properties, including a widely reported anti-cancer effect. The present review focuses on the different known mechanisms partaking in said anti-tumour effects, with particular emphasis on breast cancer. Their structure and reactivity allows flavonoids to work as antioxidant agents and phyto-oestrogens, modulating oestrogen signalling and metabolism to induce an overall anti-proliferative response. Other effects include the ability of flavonoids to modulate the CYP1 (cytochrome P450 1) and ABC (ATP-binding cassette) protein families, involved in carcinogenesis and drug delivery respectively. They can also induce apoptosis and cell cycle arrest and regulate other signalling pathways involved in the development and progression of cancer. In conclusion, there is accumulating evidence on the versatility of flavonoids and the numerous activities contributing to their anti-tumour effect. The complex, yet effective, mechanism of action of flavonoids, together with their interesting pharmacological properties, is the basis for their potential application in breast and other cancers. This rationale has led to the current interest in the application of flavonoids, including clinical trials currently underway and the development of novel flavonoids with improved properties, which hold great promise for tackling breast cancer.

scholarly journals Dynamic modelling of oestrogen signalling and cell fate in breast cancer cells

2011 ◽  
Vol 11 (7) ◽  
pp. 523-532 ◽  
Author(s):  
John J. Tyson ◽  
William T. Baumann ◽  
Chun Chen ◽  
Anael Verdugo ◽  
Iman Tavassoly ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Fate ◽  
Breast Cancer Cells ◽  
Dynamic Modelling ◽  
Oestrogen Signalling

scholarly journals A-kinase anchoring protein BIG3 coordinates oestrogen signalling in breast cancer cells

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Tetsuro Yoshimaru ◽  
Masaya Ono ◽  
Yoshimi Bando ◽  
Yi-An Chen ◽  
Kenji Mizuguchi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Anchoring Protein ◽  
Oestrogen Signalling

scholarly journals Analysis of genomic and non-genomic signalling of oestrogen receptor in PDX models of breast cancer treated with a combination of the PI3K inhibitor Alpelisib (BYL719) and fulvestrant

2020 ◽  
Author(s):  
Muriel Le Romancer ◽  
Julien Jacquemetton ◽  
Loay Kassem ◽  
Coralie Poulard ◽  
Ahmed Dahmani ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Target Genes ◽  
Treated Patient ◽  
Tumour Response ◽  
Pi3k Inhibitor ◽  
Proximity Ligation Assay ◽  
Proximity Ligation ◽  
Oestrogen Signalling ◽  
Pdx Models

Abstract Background Endocrine therapies targeting oestrogen signalling have significantly improved breast cancer (BC) patient survival, although 40% of ERα-positive BCs do not respond to those therapies. Aside from genomic signalling, oestrogen triggers non-genomic pathways by forming a complex containing methylERα/Src/PI3K, a hallmark of aggressiveness and resistance to tamoxifen. We aimed to confirm the prognostic value of this complex and investigated whether its targeting could improve tumour response in vivo.Methods The interaction of ERα/Src and ERα/PI3K was studied by proximity ligation assay (PLA) in a cohort of 440 BC patients. We then treated patient-derived BC xenografts (PDXs) with fulvestrant or the PI3K inhibitor alpelisib (BYL719) alone or in combination. We analysed their anti-proliferative effects on 6 ERα + and 3 ERα- PDX models. Genomic and non-genomic oestrogen signalling were assessed by measuring ERα/PI3K interaction by PLA or the expression of key oestrogen target genes by RT-QPCR, respectively.Results We confirmed that ERα/Src and especially ERα/PI3K interaction were associated with a trend to poorer survival. In ERα + tumours, the combination of BYL719 and fulvestrant was more effective than fulvestrant alone in 3 models, irrespective of PI3K, PTEN status or ERα/PI3K targeting. Interestingly, in some ERα- models, fulvestrant alone impacted tumour growth and this was associated with a decrease in ERα/PI3K interaction.Conclusions Our results demonstrate that ERα/PI3K may constitute a new prognostic marker, as well as a new target in BC. Indeed, resistance to fulvestrant was clearly associated with a lack of ERα/PI3K targeting in the cytoplasm.

scholarly journals The complex nature of oestrogen signalling in breast cancer: enemy or ally?

2016 ◽  
Vol 36 (3) ◽  
Author(s):  
Yulia Lipovka ◽  
John P. Konhilas
Keyword(s):  
Breast Cancer ◽  
Molecular Mechanisms ◽  
Potential Outcomes ◽  
Cancer Growth ◽  
Complex Nature ◽  
Dual Effect ◽  
Unique Role ◽  
Specific Receptors ◽  
Potential Impact ◽  
Oestrogen Signalling

The pleiotropic nature of oestradiol, the main oestrogen found in women, has been well described in the literature. Oestradiol is positioned to play a unique role since it can respond to environmental, genetic and non-genetic cues to affect genetic expression and cellular signalling. In breast cancer, oestradiol signalling has a dual effect, promoting or inhibiting cancer growth. The potential impact of oestradiol on tumorigenesis depends on the molecular and cellular characteristics of the breast cancer cell. In this review, we provide a broad survey discussing the cellular and molecular consequences of oestrogen signalling in breast cancer. First, we review the structure of the classical oestrogen receptors and resultant transcriptional (genomic) and non-transcriptional (non-genomic) signalling. We then discuss the nature of oestradiol signalling in breast cancer including the specific receptors that initiate these signalling cascades as well as potential outcomes, such as cancer growth, proliferation and angiogenesis. Finally, we examine cellular and molecular mechanisms underlying the dimorphic effect of oestrogen signalling in breast cancer.

scholarly journals Role of sphingolipids in oestrogen signalling in breast cancer cells: an update

2013 ◽  
Vol 220 (3) ◽  
pp. R25-R35 ◽  
Author(s):  
O Sukocheva ◽  
C Wadham
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Second Messengers ◽  
Membrane Receptors ◽  
Future Research ◽  
Specific Effects ◽  
Oestrogen Signalling ◽  
Signalling Cascade

The signaling pathways activated by the steroid hormone oestrogen include a variety of cytoplasmic second messengers linked to a multitude of tissue-specific effects. In the last decade, sphingolipids and their membrane receptors were added to the list of oestrogen-activated mediators. Oestrogen triggers the sphingolipid signalling cascade in various tissues including breast cancer. Extensive research has shown that sphingolipids are the key regulatory molecules in growth factor networks. Sphingolipids can control the rate of cell proliferation and the differentiation outcome during malignant transformation. In this study, we summarise novel experimental evidences linking sphingolipids to oestrogen-activated effects, highlight the role of sphingolipids in cancer cells and discuss new avenues for future research at the intersection between oestrogen and sphingolipid signalling.

Downstream targets of growth factor and oestrogen signalling and endocrine resistance: the potential roles of c-Myc, cyclin D1 and cyclin E

2005 ◽  
Vol 12 (Supplement_1) ◽  
pp. S47-S59 ◽  
Author(s):  
Alison J Butt ◽  
Catriona M McNeil ◽  
Elizabeth A Musgrove ◽  
Robert L Sutherland
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cyclin D1 ◽  
Cell Cycle Progression ◽  
Cyclin E ◽  
Endocrine Resistance ◽  
Cycle Progression ◽  
Er Positive ◽  
Oestrogen Signalling

Antioestrogen therapy is a highly effective treatment for patients with oestrogen-receptor (ER)-positive breast cancer, emphasising the central role of oestrogen action in the development and progression of this disease. However, effective antioestrogen treatment is often compromised by acquired endocrine resistance, prompting the need for a greater understanding of the down-stream mediators of oestrogen action that may contribute to this effect. Recent studies have demonstrated a critical link between oestrogen’s mitogenic effects and cell cycle progression, particularly at the G1 to S transition where key effectors of oestrogen action are c-Myc and cyclin D1, which converge on the activation of cyclin E-cdk2. These components are rapidly upregulated in response to oestrogen, and can mimic its actions on cell cycle progression, including re-initiating cell proliferation in antioestrogen-arrested cells. Here we review the roles of c-Myc, cyclin D1 and cyclin E in oestrogen action and endocrine resistance, and identify their potential as markers of disease progression and endocrine responsiveness, and as novel therapeutic targets in endocrine-resistant breast cancer.

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