Up-regulation of LRP16 mRNA by 17beta-estradiol through activation of estrogen receptor alpha (ERalpha), but not ERbeta, and promotion of human breast cancer MCF-7 cell proliferation: a preliminary report.

2003 ◽  
pp. 217-224 ◽  
Author(s):  
W-D Han ◽  
Y-M Mu ◽  
X-C Lu ◽  
Z-M Xu ◽  
X-J Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Estrogen Receptor ◽  
Blot Analysis ◽  
Estrogen Receptor Alpha ◽  
Cyclin E ◽  
Expression Level ◽  
Receptor Alpha ◽  
Mcf 7

LRP16 is a novel gene cloned from lymphocytic cells, and its function is not known. The expression level of LRP16 mRNA was up-regulated by estrogen in breast cancer MCF-7 cells based on the computed aided serial analysis of gene expression (SAGE) analysis. In this study, we investigate the effect of 17beta-estradiol (17beta-E(2)) on the expression of LRP16 mRNA and the effects of overexpression of LRP16 on the proliferation of cultured MCF-7 cells and the possible mechanisms involved. The expression level of LRP16 mRNA induced by 17beta-E(2) was determined by Northern blot analysis. LRP16 promoter-controlled luciferase expression vector (pGL3-S(0)) was co-transfected with various nuclear receptors, including estrogen receptor alpha and beta (ERalpha and ERbeta), glucocorticoid receptor alpha (GRalpha), androgen receptor (AR) and peroxisome-proliferator activated receptor gamma and alpha (PPARgamma and PPARgamma) into COS-7 cells, and the relative luciferase activity was measured using Dual-luciferase report assay systems. The effect of overexpression of LRP16 on MCF-7 proliferation was examined by the Trypan Blue exclusion method, and the cell cycle was analyzed by flow cytometry. The expression levels of cyclin E, p53 and p21(WAF1/CIP1) proteins were determined by Western blot analysis. The results showed (1) 17beta-E(2) induced a five- to eightfold increase in LRP16 mRNA levels in MCF-7 cells; (2) the relative luciferase activities in the COS-7 cells co-transfected by pGL3-S(0) and ERalpha or AR were 7.8-fold and 11-fold respectively of those in the control cells transfected by pGL3-S(0) alone; (3) overexpression of LRP16 stimulated MCF-7 cell proliferation, and the numbers of cells in the S-phase of the cell cycle in cells transfected with LRP16 increased about 10% compared with the control cells; and (4) cyclin E levels were much higher in cells with overexpression of LRP16 than in the control cells, while the expression levels of p53 and p21(WAF1/CIP1) were not different between the two groups of cells. From these results we concluded that estrogen up-regulates the expression level of LRP16 mRNA through activation of ERalpha and that overexpression of LRP16 promotes MCF-7 cell proliferation probably by increasing cyclin E.

Knockdown of ZBTB7A inhibits cell proliferation of breast cancer through regulating the ubiquitination of estrogen receptor alpha

Life Sciences ◽  
2019 ◽  
Vol 239 ◽  
pp. 117042 ◽  
Author(s):  
Xiao Xiao ◽  
Yingying Shen ◽  
Liyang Yin ◽  
Jun He ◽  
Xiaoyu Ni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Estrogen Receptor ◽  
Estrogen Receptor Alpha ◽  
Receptor Alpha

In silico Molecular Modelling of Selected Natural Ligands and their Binding Features with Estrogen Receptor Alpha

2018 ◽  
Vol 15 (1) ◽  
pp. 89-96 ◽  
Author(s):  
V.L. Maruthanila ◽  
R. Elancheran ◽  
Nand Kishor Roy ◽  
Anupam Bhattacharya ◽  
Ajaikumar B. Kunnumakkara ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cell Line ◽  
In Silico ◽  
Estrogen Receptor Alpha ◽  
Natural Compounds ◽  
Pharmacokinetic Parameters ◽  
Anticancer Activities ◽  
Receptor Alpha ◽  
Mcf 7

Background: Breast cancer is one of the most common cancers diagnosed among women. It is now recognized that two receptors mediate estrogen action and the presence of estrogen receptor alpha (ER&#945;) correlates with better prognosis and the likelihood of response to hormonal therapy. ER&#945; is an attractive target for the treatment of breast cancer. Most of the drugs currently used for the breast cancer treatment have numerous side effects and they are often unsuccessful in removing the tumour completely. Hence, we focused on natural compounds like flavonoids, polyphenols, etc. which do not exhibit any high toxic effects against normal cells. </P><P> Objectives: To identify the potential natural inhibitors for BCa through an optimised in silico approach. </P><P> Methods: Structural modification and molecular docking-based screening approaches were imposed to identify the novel natural compounds by using Schrödinger (Maestro 9.5). The Qikprop v3.5 was used for the evaluation of important ADME parameters and its permissible ranges. Cytotoxicity of the compounds was evaluated by MTT assay against MCF-7 Cell lines. Results: From the docking studies, we found that the compounds, Myricetin, Quercetin, Apigenin, Luteolin and Baicalein showed the highest Glide Scores -10.78, -9.48, -8.92, -8.87 and -8.82 kcal mol-1 respectively. Of these, Luteolin and Baicalein showed the significant IC50 values (25 &#177; 4.0 and 58.3 &#177; 4.4 &#181;M, respectively) against MCF-7 cell line. The ADME profiling of the test compounds was evaluated to find the drug-likeness and pharmacokinetic parameters. We mainly focused on in silico study to dock the compounds into the human estrogen receptor ligand binding domain (hERLBD) and compare their predicted binding affinity with known antiestrogens. Myricetin, Quercetin, Apigenin, Luteolin and Baicalein were identified as the most promising among all. Of these, Luteolin and Baicalein showed significant anticancer activities against MCF-7 cell line. These findings may provide basic information for the development of anti-breast cancer agents.

scholarly journals Tetrahydro-iso-alpha Acids Antagonize Estrogen Receptor Alpha Activity in MCF-7 Breast Cancer Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Maëlle Lempereur ◽  
Claire Majewska ◽  
Amandine Brunquers ◽  
Sumalee Wongpramud ◽  
Bénédicte Valet ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Estrogen Receptor Alpha ◽  
Foam Stability ◽  
Binding Motif ◽  
Brewing Industry ◽  
Receptor Alpha ◽  
Mcf 7

Tetrahydro-iso-alpha acids commonly called THIAA or Tetra are modified hop acids extracted from hop (Humulus lupulusL.) which are frequently used in brewing industry mainly in order to provide beer bitterness and foam stability. Interestingly, molecular structure of tetrahydro-iso-alpha acids is close to a new type of estrogen receptor alpha (ERα) antagonists aimed at disrupting the binding of coactivators containing an LxxLL motif (NR-box). In this work we show that THIAA decreases estradiol-stimulated proliferation of MCF-7 (ERα-positive breast cancer cells). Besides, we show that it inhibits ERαtranscriptional activity. Interestingly, this extract fails to compete with estradiol for ERαbinding and does not significantly impact the receptor turnover rate in MCF-7 cells, suggesting that it does not act like classical antiestrogens. Hence, we demonstrate that THIAA is able to antagonize ERαestradiol-induced recruitment of the LxxLL binding motif.

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