scholarly journals Genome-Wide Investigation of Genes Regulated by ERα in Breast Cancer Cells

Molecules ◽  
2018 ◽  
Vol 23 (10) ◽  
pp. 2543 ◽  
Author(s):  
Shuning Wang ◽  
Xiaoju Li ◽  
Wangqian Zhang ◽  
Yuan Gao ◽  
Kuo Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor Alpha ◽  
Microarray Dataset ◽  
Rna Seq ◽  
Bioinformatics Analyses ◽  
Genome Wide ◽  
Breast Cancer Growth ◽  
The Relationship ◽  
Proliferation And Invasion ◽  
Mcf 7

Estrogen receptor alpha (ERα), which has been detected in over 70% of breast cancer cases, is a driving factor for breast cancer growth. For investigating the underlying genes and networks regulated by ERα in breast cancer, RNA-seq was performed between ERα transgenic MDA-MB-231 cells and wild type MDA-MB-231 cells. A total of 267 differentially expressed genes (DEGs) were identified. Then bioinformatics analyses were performed to illustrate the mechanism of ERα. Besides, by comparison of RNA-seq data obtained from MDA-MB-231 cells and microarray dataset obtained from estrogen (E2) stimulated MCF-7 cells, an overlap of 126 DEGs was screened. The expression level of ERα was negatively associated with metastasis and EMT in breast cancer. We further verified that ERα might inhibit metastasis by regulating of VCL and TNFRSF12A, and suppress EMT by the regulating of JUNB and ID3. And the relationship between ERα and these genes were validated by RT-PCR and correlation analysis based on TCGA database. By PPI network analysis, we identified TOP5 hub genes, FOS, SP1, CDKN1A, CALCR and JUNB, which were involved in cell proliferation and invasion. Taken together, the whole-genome insights carried in this work can help fully understanding biological roles of ERα in breast cancer.

scholarly journals Identification and Analysis of Estrogen Receptor α Promoting Tamoxifen Resistance-Related lncRNAs

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Xiulei Zhang ◽  
Shanjun Gao ◽  
Zhen Li ◽  
Wei Wang ◽  
Guangzhi Liu
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Patients ◽  
Estrogen Receptor Alpha ◽  
Acquired Resistance ◽  
Tamoxifen Resistance ◽  
Estrogen Receptor Α ◽  
Rna Seq ◽  
Breast Cancer Patients ◽  
Mcf 7

70-75% breast cancer patients are estrogen receptor alpha positive (ERα+), and the antiestrogen drug tamoxifen has been used for the past three decades. However, in 20-30% of these patients, tamoxifen therapy fails due to intrinsic or acquired resistance. A previous study has showed ERα signaling still exerts significant roles in the development of tamoxifen resistance and several lncRNAs have been demonstrated important roles in tamoxifen resistance. But ERα directly regulated and tamoxifen resistance related lncRNAs remain to be discovered. We reanalyze the published ERα chromatin immunoprecipitation-seq (ChIP-seq) and RNA-seq data of tamoxifen-sensitive (MCF-7/WT) and tamoxifen-resistant (MCF-7/TamR) breast cancer cells. We demonstrate that there are differential ERα recruitment events and the differentials may alert the expression profile in MCF-7/WT and MCF-7/TamR cells. Furthermore, we make an overlap of the ERα binding lncRNAs and differentially expressed lncRNAs and get 49 ERα positively regulated lncRNAs. Among these lncRNAs, the expression levels of AC117383.1, AC144450.1, RP11-15H20.6, and ATXN1-AS1 are negatively correlated with the survival probability of breast cancer patients and ELOVL2-AS1, PCOLCE-AS1, ITGA9-AS1, and FLNB-AS1 are positively correlated. These lncRNAs may be potential diagnosis or prognosis markers of tamoxifen resistance.

scholarly journals Expression Patterns of Immune Checkpoints in Breast Cancer Patients

2021 ◽  
Author(s):  
Dan Qiu ◽  
Xianxin Yan ◽  
Guijuan Zhang ◽  
Xinqin Xiao ◽  
Jingyu Cao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Checkpoint Inhibitors ◽  
Expression Patterns ◽  
Microarray Dataset ◽  
Tissue Expression ◽  
Immune Checkpoints ◽  
Rna Seq ◽  
Breast Cancer Patients ◽  
Insight Into ◽  
Mcf 7

Abstract Background: immunotherapy with immune checkpoint inhibitors (ICIs) for solid tumors had significantly improved overall survival (OS). Positive response to PD-1/PD-L1 blockades was observed in the treatment of solidtumors. Breast cancer (BC) patients are no exception. However, the efficacy of immunocheckpoint therapy in BC patients remains poor. A particularly important factor is the lack of studies on the expression patterns of immune checkpoints in BC patients. Method: in this study, the microarray dataset GSE10810 was downloaded from the Gene Expression Database Synthesis (GEO) to analyze the differential expression of BC genes and perform GO and KEGG analysis. Then, we explored theprognostic value of ICs for BC patients by analyzing RNA-seq and mutation data from 657 BC patients from theCancer Genome Atlas (TCGA) database. Next, we analyzed the differences in the expression of relevant immune checkpoints between 1085 BC patients and 291 healthy controls (HC) in the Genotype-Tissue Expression (GTEx) database. Finally, we analyzed the expression levels of IFNγ-R, PD-L1, STAT1, IDO and other genes in MCF-10A, MF-10AT, MCF-7, MDA-MB-231 cell lines.Results: It was found that increased expression of PD-1, PD-L1, STAT1, CTLA-4 was associated with poor OS in BC patients. In addition, co-expression of PD-L1 with PD-1, STAT1or CTLA-4 and co-expression of PD-1 with CTLA-4was related to poor OS. We analyzed associations between the proportionate expression of PD-L1 and PD-1, PD-L1 and STAT1, PD-1 and CTLA-4, PD-1 and LAG3, PD-L1 and CTLA-4 in BC patients, there was significance in correlation in both of the BC patients.The expression of STAT1 in BC patients was compared with that of HC, and it was found that STAT1 was highly expressed in BC patients. Conclusions: our results suggest that transcriptome-based co-expression of STAT1 and PD-L1 is a predictor for poor OS in BC patients, which might provide novel insight into designing combinational targeted therapy for BC.

scholarly journals MiR-940 promotes malignant progression of breast cancer by regulating FOXO3

2020 ◽  
Vol 40 (9) ◽  
Author(s):  
Huayao Zhang ◽  
Jingwen Peng ◽  
Jianguo Lai ◽  
Haiping Liu ◽  
Zhiyuan Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Colony Formation ◽  
Target Gene ◽  
Luciferase Reporter Assay ◽  
Luciferase Reporter ◽  
Reporter Assay ◽  
Poor Survival ◽  
High Level ◽  
The Relationship ◽  
Proliferation And Invasion

Abstract Breast cancer (BC) is a common cancer with poor survival. The present study aimed to explore the effect of miR-940 on the process of BC cells and its target gene FOXO3. The expression of miR-940 was assessed in BC tissues and cells using qRT-PCR. Furthermore, the correlation between miR-940 and prognosis of BC patients from the TCGA database was analyzed. CCK8 assays and colony formation assays were used to explore the effect of miR-940 on BC cell proliferation. The invasion abilities were detected by transwell assays. Luciferase reporter assay was performed to scrutinize the relationship between miR-940 and FOXO3. Finally, rescue experiments were performed through FOXO3 down-regulation and miR-940 inhibitors by using CCK8 assays, colony formation assays and transwell assays. miR-940 was significantly up-regulated in BC cells and tissues. In addition, the high level of miR-940 correlated with poor survival of BC patients (P=0.023). CCK8 assays, colony formation assays and transwell assays indicated that miR-940 promoted the proliferation and invasion abilities of BC cells. The luciferase reporter assay suggested that miR-940 directly targeted FOXO3. Moreover, we found that the effect of si-FOXO3 was rescued by miR-940 inhibitors in BC cells. miR-940 may promote the proliferation and invasion abilities of BC cells by targeting FOXO3. Our study suggested that miR-940 could be a novel molecular target for therapies against BC.

scholarly journals Integration of RNA-seq and Ribosome Profiling to Characterize Transcriptional and Translational Estrogen Responses of Genes in Human Breast Cancer

2020 ◽  
Author(s):  
Siew Woh Choo ◽  
Yu Zhong ◽  
Edward Sendler ◽  
Anton Scott Goustin ◽  
Juan Cai ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Estrogen Receptor Alpha ◽  
Ribosome Profiling ◽  
Estrogen Treatment ◽  
Differentially Expressed ◽  
Significant Advance ◽  
Rna Seq ◽  
Protein Coding ◽  
Receptor Alpha

Abstract BackgroundEstrogen is a hormone that is frequently essential in breast cancer to drive key transcriptional programs by interacting with the estrogen receptor alpha that upregulates proliferative and oncogenic genes and represses apoptotic and tumor suppressor genes. Protein-coding targets of estrogen regulation in breast cancer are well-defined. However, long non-coding RNA (lncRNA) genes account for the majority of human gene catalogs. The coding status of these genes – their accidental, or regulated, translation by ribosomes, under the influence of estrogen – remains a controversial topic. MethodsHere, we performed comprehensive transcriptome analysis using RNA-Seq, as well as ribosome profiling using Ribo-Seq, on the same samples: biological replicates of human estrogen receptor alpha (ERa) positive MCF7 breast cancer cells before and after estrogen treatment. We correlated these two datasets, globally highlighting protein-coding and lncRNA differentially expressed genes and transcripts that were positively as well as negatively responsive to estrogen, separately at the transcriptional level and the translational (as approximated by ribosome binding) level.ResultsOur data showed that some transcripts were more robustly detected in RNA-Seq than in the ribosome-profiling data, and vice versa, suggesting distinct gene-specific estrogen responses at the transcriptional and the translational level, respectively. Certain differentially expressed transcripts may point to the regulation of alternative splicing by estrogen. Several pseudogenes were co- and anti-regulated with their cancer-functional parental genes. Gene ontology analysis highlighted cancer-relevant pathways enriched after estrogen treatment in cells.ConclusionsOur study represents a significant advance in the estrogen receptor biology, because we demonstrated global effects of estrogen on splicing and translation that are distinct from, and not always correlated with, its effects on transcription, and that differ globally for protein-coding and lncRNA genes. We have also highlighted for the first time the transcriptional and translational response of expressed pseudogenes to estrogen, pointing to new perspectives for biomarker and drug-target development for breast cancer in future.

Partial agonist, but not pure antiestrogens stimulate doming, a marker of normal differentiation, in the MCF-7 breast cancer cell line

2012 ◽  
Vol 12 (3) ◽  
Author(s):  
W. Barkley Butler ◽  
Stephen C. D’Amico ◽  
William J. Glassford ◽  
Weizhen Wu
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Estrogen Receptor Alpha ◽  
Partial Agonist ◽  
Trichostatin A ◽  
Calf Serum ◽  
Cancer Cell Line ◽  
Dependent Manner ◽  
Dome Formation ◽  
Mcf 7

AbstractThe mechanisms by which tamoxifen inhibits breast tumor growth are not completely understood. Partial agonist antiestrogens such as tamoxifen may cause the estrogen receptor (ER) to interact with genes different from those activated by ER bound to estradiol. Doming is a property often associated with, and considered a marker of, differentiation in mammary epithelial cells in culture. This study compared the ability of pure and partial agonist antiestrogens to stimulate doming.MCF-7 cells grown in medium with 10% calf serum were treated with antiestrogens. Domes were counted in three rows (width of the 4× field) across the flask.Three partial agonist antiestrogens [4-hydroxytamoxifen (OHT), H1285 and RU 39,411] caused dome formation. None of the pure antiestrogens tested (ICI 164,384, ICI 182,780 and RU 58,668) caused doming. Doming was stimulated in a dose-dependent manner starting at 1 nM OHT with maximum stimulation at 10–100 nM. Estradiol did not stimulate doming, but blocked doming at 1%–10% of the OHT concentration. Trichostatin A (TSA) reduced the level of estrogen receptor alpha (ERα) and adding it 24 h before adding OHT prevented dome formation.OHT and the other partial agonist antiestrogens appear to act through the ER to stimulate doming. The ability of tamoxifen to induce a marker of differentiation may play a role in its inhibition of breast tumors. If so, then the fact that other partial agonist antiestrogens share this ability, but that pure antiestrogens lack it, may be an important consideration in developing new antiestrogens for breast cancer therapy.

Correlation between Changes in Prolactin and Melatonin Serum Levels after Radical Mastectomy

1987 ◽  
Vol 73 (3) ◽  
pp. 263-267 ◽  
Author(s):  
Paolo Lissoni ◽  
Franco Paolorossi ◽  
Sandro Barni ◽  
Gabriele Tancini ◽  
Sergio Crispino ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Stage ◽  
Radical Mastectomy ◽  
Serum Levels ◽  
Axillary Node ◽  
Neoplastic Disease ◽  
Before And After ◽  
Node Involvement ◽  
Breast Cancer Growth ◽  
The Relationship

Both prolactin (PRL) and melatonin (MLT) (the most important pineal hormone) have been shown to play a role in regulating breast cancer growth. The present study was carried out to investigate the relationship between PRL and MLT secretions in human breast cancer. Twenty-four women with breast cancer, at clinical stage T1-2 N0-2 M0, were evaluated before and after radical mastectomy. As controls, 14 women who underwent surgery for reasons other than neoplastic disease were included in the study. PRL and MLT serum levels were measured by RIA before and 15 days after surgery. There were no significant differences in mean PRL serum levels between patients and controls; mean MLT serum values were significantly higher in patients than in controls. In no control subject was PRL affected by surgery. In contrast, 13/24 breast cancer women showed high PRL levels after mastectomy; the PRL rise induced by surgery was significantly higher in patients without axillary node involvement. MLT was not affected by mastectomy in 13 patients, whereas it was enhanced in 5 women and decreased in the last 6 cases. No significant correlation was seen between PRL and MLT changes induced by mastectomy. The present study shows that radical mastectomy influences PRL and MLT secretions, however, its clinical significance remains to be established.

HIF-1α Promotes Breast Cancer Cell MCF-7 Proliferation and Invasion Through Regulating miR-210

2017 ◽  
Vol 32 (8) ◽  
pp. 297-301 ◽  
Author(s):  
Yang Zhang ◽  
Jinyin Yan ◽  
Lu Wang ◽  
Hao Dai ◽  
Ning Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Proliferation And Invasion ◽  
Mcf 7
Sign in / Sign up

Export Citation Format

Share Document