scholarly journals A Role for ER-Beta in the Effects of Low-Density Lipoprotein Cholesterol and 27-Hydroxycholesterol on Breast Cancer Progression: Involvement of the IGF Signalling Pathway?

Cells ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 94
Author(s):  
Reham M. Mashat ◽  
Hanna A. Zielinska ◽  
Jeff M. P. Holly ◽  
Claire M. Perks
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Oestrogen Receptor ◽  
Breast Cancer Cells ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Migration And Invasion ◽  
Low Density ◽  
Igf I ◽  
Positive Breast Cancer

Cholesterol—in particular, high levels of low-density lipoprotein (LDL) and its metabolite, 27-hydroxycholesterol (27-OHC)—is correlated with increases in the risks of breast cancer and obesity. Although the high expression of LDL/27-OHC has been reported in breast cancer, its effects and mechanism of action remain to be fully elucidated. In this study, we found that the effects of LDL on cell proliferation were mediated by the activation of the cytochrome P450 enzyme, sterol 27 hydroxylase, and cholesterol 27-hydroxylase (CYP27A1) in both ER-α-positive and ER-α-negative breast cancer cells. We found that treatment with 27-OHC only increased cell growth in oestrogen receptor-α (ER-α)-positive breast cancer cells in an ER-α-dependent manner, but, interestingly, the effects of 27-OHC on cell migration and invasion were independent of ER-α. Using ER-α-negative MDA-MB-231 cells, we found that 27-OHC similarly promoted cell invasion and migration, and this was mediated by oestrogen receptor β (ER-β). These results suggest that 27-OHC promotes breast cancer cell proliferation in ER-α-positive breast cancer cells via ER-α, but migration and invasion are mediated via ER-β in ER-α positive and negative cell lines. The addition of LDL/27OHC increased the production of IGF-I and the abundance of IGF-IR in TNBC. We further found that modulating ER-β using an agonist or antagonist increased or decreased, respectively, levels of the IGF-I and EGF receptors in TNBC. The inhibition of the insulin-like growth factor receptor blocked the effects of cholesterol on cell growth and the migration of TNBC. Using TCGA and METABRIC microarray expression data from invasive breast cancer carcinomas, we also observed that higher levels of ER-beta were associated with higher levels of IGF-IR. Thus, this study shows novel evidence that ER-β is central to the effects of LDL/27OHC on invasion, migration, and the IGF and EGF axes. Our data suggest that targeting ER-β in TNBC could be an alternative approach for downregulating IGF/EGF signalling and controlling the impact of LDL in breast cancer patients.

scholarly journals Fulvestrant-induced expression of ErbB3 and ErbB4 receptors sensitizes oestrogen receptor-positive breast cancer cells to heregulin β1

2011 ◽  
Vol 13 (2) ◽  
Author(s):  
Iain R Hutcheson ◽  
Lindy Goddard ◽  
Denise Barrow ◽  
Richard A McClelland ◽  
Hayley E Francies ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Oestrogen Receptor ◽  
Breast Cancer Cells ◽  
Induced Expression ◽  
Positive Breast Cancer

scholarly journals Estimating the effect of lipids on IGF axis and subsequent breast cancer risk

2020 ◽  
Author(s):  
Vanessa Y Tan ◽  
Caroline J Bull ◽  
Kalina M Biernacka ◽  
Alexander Teumer ◽  
Laura Corbin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factors ◽  
Mendelian Randomization ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Weak Instruments ◽  
Igf I ◽  
Igfbp 3 ◽  
Insulin Like Growth Factors

AbstractCirculating lipids have been associated with breast cancer (BCa). This association may, in part, be due to an effect of lipids on insulin-like growth factors (IGFs), which have been reliably associated with BCa. In two-sample Mendelian randomization (MR) analyses, we found that low density lipoprotein (LDL-C) was associated with IGFBP-3 (beta:0.08 SD; 95%CI:0.02,0.15; p = 0.01, per SD increase in LDL-C) and IGFBP-3 was associated with postmenopausal BCa (OR:1.09; 95%CI:1.00,1.19; p = 0.05, per SD increase in IGFBP-3). We also found that triglycerides were associated with IGF-I (beta:-0.13SD; 95%CI:-0.22,-0.03, per SD increase in triglycerides) and that IGF-I was associated with overall BCa (OR:1.10;95%CI:1.02,1.18, per SD increase in IGF-I). Taken together, these results suggest that IGFBP-3 may be a potential causal step between LDL-C and postmenopausal BCa and IGF-I a potential causal for triglycerides. Our two-step MR results build on evidence linking circulating lipids and IGFs with BCa, however, multivariable MR analyses are currently unable to support this relationship due to weak instruments.

IL-6 Triggers the Migration and Invasion of Oestrogen Receptor-Negative Breast Cancer Cells via Regulation of Hippo Pathways

2018 ◽  
Vol 123 (5) ◽  
pp. 549-557 ◽  
Author(s):  
Lingmi Hou ◽  
Shaoli Xie ◽  
Guanwu Li ◽  
Bin Xiong ◽  
Yanchun Gao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Oestrogen Receptor ◽  
Breast Cancer Cells ◽  
Migration And Invasion

Glucocorticoids induce CCN5/WISP-2 expression and attenuate invasion in oestrogen receptor-negative human breast cancer cells

2012 ◽  
Vol 447 (1) ◽  
pp. 71-79 ◽  
Author(s):  
Nathalie Ferrand ◽  
Emilien Stragier ◽  
Gérard Redeuilh ◽  
Michèle Sabbah
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Oestrogen Receptor ◽  
Breast Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Integration Site ◽  
Tissue Growth ◽  
Glucocorticoid Treatment ◽  
Mesenchymal Transition ◽  
Positive Breast Cancer

CCN5 (cysteine-rich 61/connective tissue growth factor/nephroblastoma overexpressed 5)/WISP-2 [WNT1 (wingless-type MMTV integration site family, member 1)-inducible signalling pathway protein 2] is an oestrogen-regulated member of the CCN family. CCN5 is a transcriptional repressor of genes associated with the EMT (epithelial–mesenchymal transition) and plays an important role in maintenance of the differentiated phenotype in ER (oestrogen receptor)-positive breast cancer cells. In contrast, CCN5 is undetectable in more aggressive ER-negative breast cancer cells. We now report that CCN5 is induced in ER-negative breast cancer cells such as MDA-MB-231 following glucocorticoid exposure, due to interaction of the endogenous glucocorticoid receptor with a functional glucocorticoid-response element in the CCN5 gene promoter. Glucocorticoid treatment of MDA-MB-231 cells is accompanied by morphological alterations, decreased invasiveness and attenuated expression of mesenchymal markers, including vimentin, cadherin 11 and ZEB1 (zinc finger E-box binding homeobox 1). Interestingly, glucocorticoid exposure did not increase CCN5 expression in ER-positive breast cancer cells, but rather down-regulated ER expression, thereby attenuating oestrogen pathway signalling. Taken together, our results indicate that glucocorticoid treatment of ER-negative breast cancer cells induces high levels of CCN5 expression and is accompanied by the appearance of a more differentiated and less invasive epithelial phenotype. These findings propose a novel therapeutic strategy for high-risk breast cancer patients.

Exploration of mechanisms of α-linolenic acid in reducing the growth of oestrogen receptor positive breast cancer cells (MCF-7)

2016 ◽  
Vol 24 ◽  
pp. 513-519 ◽  
Author(s):  
Julie K. Mason-Ennis ◽  
Lauren P. LeMay-Nedjelski ◽  
Ashleigh K.A. Wiggins ◽  
Lilian U. Thompson
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Linolenic Acid ◽  
Oestrogen Receptor ◽  
Breast Cancer Cells ◽  
Mcf 7 ◽  
Positive Breast Cancer
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