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 Estrogen receptor α geneESR1amplification may predict endocrine therapy responsiveness in breast cancer patients

2009 ◽  
Vol 100 (6) ◽  
pp. 1012-1017 ◽  
Author(s):  
Saori Tomita ◽  
Zhenhuan Zhang ◽  
Masahiro Nakano ◽  
Mutsuko Ibusuki ◽  
Teru Kawazoe ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Patients ◽  
Endocrine Therapy ◽  
Estrogen Receptor Α ◽  
Breast Cancer Patients

scholarly journals Phosphorylation of Estrogen Receptor-α at Ser167 Is Indicative of Longer Disease-Free and Overall Survival in Breast Cancer Patients

2007 ◽  
Vol 13 (19) ◽  
pp. 5769-5776 ◽  
Author(s):  
Jie Jiang ◽  
Naveed Sarwar ◽  
David Peston ◽  
Elena Kulinskaya ◽  
Sami Shousha ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Estrogen Receptor ◽  
Cancer Patients ◽  
Estrogen Receptor Α ◽  
Breast Cancer Patients ◽  
Disease Free

Translational cell study exploring the role of estrogen receptor β expression as a predictive and/or prognostic factor in breast cancer patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22185-e22185
Author(s):  
S. Saji ◽  
N. Honma ◽  
M. Hirose ◽  
S. Hayashi ◽  
K. Kuroi
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cell Line ◽  
Cancer Patients ◽  
Triple Negative ◽  
Breast Cancer Patients ◽  
Her 2 ◽  
Mcf 7 ◽  
Cell Study ◽  
Positive Breast Cancer

e22185 Background: We have reported that positive expression of Estrogen receptor β (ERβ) was associated with better prognosis in the early breast cancer patients treated with adjuvant tamoxifen monotherapy (J Clin Oncol. 2008). In addition, this was also true in the ERα-negative/PR-negative/Her-2 negative patients. We explored the biological impact of ERβ in breast cancer cell lines to determine whether these observations were due to its prognostic power or predictive power of response to the therapy. Methods: Since MCF-7 cell was ERβ-negative ERα-positive cell line, we established two stable clones of MCF-7 by introducing ERβ expression vector (β-clone 1, β-clone 2) as the model of ERβ-positive ERα-positive breast cancer. MDA-MB 231 cell was used as ERβ-positive triple-negative cell line. These cells were subjected to proliferation, expression and functional analysis. Results: In western blotting, both β-clone 1 and clone 2 showed decreased expression of PR and Her-2 than parent MCF-7, although there were no differences in ERα expression. Expression of ERβ decreased estradiol (E2) induced proliferation ability and rate of cells in S-phase cycle. PPT (ERα-specific agonist) and DPN (ERβ-specific agonist) did not show any difference in response, and IC 50 for 4 OH-tamoxifen and fulvestrant did not differ among MCF-7, β-clone 1 and clone 2 (0.05–0.1 μM). Whereas, cell death due to deprivation of E2 from 1nM to 1pM was more frequently observed in ERβ-expressing clones than in parent MCF-7 cell. These cell deaths did not involve standard apoptosis pathway with caspase-3/7 activation and PARP cleavage. E2, DPN and PPT did not affect the proliferation of ERβ-positive triple negative MDA-MB 231 cell, and IC 50 for 4-OH tamoxifen was too high (8 μM) to be achieved in clinical pharmacological dose. Conclusions: From our cell study, better prognosis of ERβ-positive breast cancer patient who treated with adjuvant tamoxifen is mainly due to its own favorable biological behavior. However, this prognostic impact may include the favorable response to the treatment, when we use estrogen-deprivation therapy such as aromatase inhibitors (AIs). Additional clinical study in AI users would be required to address this issue. No significant financial relationships to disclose.

scholarly journals ELOVL2: a novel tumor suppressor attenuating tamoxifen resistance in breast cancer

2020 ◽  
Author(s):  
Dawoon Jeong ◽  
Juyeon Ham ◽  
Hyeon Woo Kim ◽  
Heejoo Kim ◽  
Hwee Won Ji ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Cancer Patients ◽  
Tumor Tissue ◽  
Tamoxifen Resistance ◽  
Colony Formation Assay ◽  
Breast Cancer Patients ◽  
Methylation Analysis ◽  
Genome Wide ◽  
Mcf 7

Abstract Background To comprehensively understand the molecular mechanism of tamoxifen resistance (TamR) acquisition by epigenetically regulated genes, it is essential to identify pivotal genes by genome-wide methylation analysis and verify their function in xenograft animal model and cancer patients. Methods The MCF-7/TamR breast cancer cell line was developed and a genome-wide methylation array was performed. The methylation and expression of ELOVL2 was validated in cultured cells, xenografted tumor tissue, and breast cancer patients by methylation-specific PCR, qRT-PCR, Western blot analysis, and immunohistochemistry. Deregulation of ELOVL2 and THEM4 was achieved using siRNA or generating stable transfectants. Tam sensitivity, cell growth, and apoptosis were monitored by colorimetric and colony formation assay and flow cytometric analysis. Pathway analysis was performed to generate networks for the differentially methylated genes in the MCF-7/TamR cells and for the differentially expressed genes in the ELOVL2-overexpressing cells. Results Genome-wide methylation analysis in the MCF-7/TamR cells identified elongation of very-long chain fatty acid protein 2 (ELOVL2) to be significantly hypermethylated and downregulated, which was further verified in the tumor tissues from TamR breast cancer patients (n = 28) compared with those from Tam-sensitive (TamS) patients (n = 33) (P < 0.001). Immunohistochemical analysis of tissues from cancer patients showed lower expression of ELOVL2 in the TamR than TamS tissues. Growth of the MCF-7/TamR cells overexpressing ELOVL2 was retarded in cell culture and also in xenograft tumor tissue. Strikingly, ELOVL2 attenuated resistance to Tam up to 70% judged by the colorimetric and colony formation assay and xenograft mouse model. ELOVL2 contributed to the recovery of Tam sensitivity by regulating a group of genes in the AKT and ERα signaling pathways, e.g., THEM4, which plays crucial roles in drug resistance. Conclusions ELOVL2 was hypermethylated and downregulated in TamR breast cancer patients compared with TamS patients. ELOVL2 is responsible for the recovery of Tam sensitivity. AKT- and ERα-hubbed networks are pivotal in ELOVL2 signaling, where THEM4 contributes to the relaying ELOVL2 signaling. This study implies that deregulation of a gene in fatty acid metabolism can lead to drug resistance, giving insight into the development of a new therapeutic strategy for drug-resistant breast cancer.

scholarly journals Increased expression of the estrogen receptor alpha, ESR1, in the tumors of breast cancer patients treated with trastuzumab.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Estrogen Receptor Alpha ◽  
Estrogen Receptor Α ◽  
Needle Aspiration ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Transcriptional Induction ◽  
Selection Of

Hormones function as growth factors, and estrogen provides growth signals to support and induce the proliferation of breast cancers (1-3). This is the basis of the use of endocrine therapies (4, 5) including tamoxifen and letrozole as first-line treatment for patients with breast cancer. We found through mining published microarray and multiplexed gene expression profiling datasets that the estrogen receptor α (ESR1) was among the genes most differentially expressed in the primary tumors and fine needle aspiration-isolated tumor cells of patients with breast cancer treated with trastuzumab. However, estrogen receptor α was expressed at higher rather than lower levels in the tumors of trastuzumab-treated patients. These data, obtained through blind, systems-level analysis of published microarray data (6-8), suggest that trastuzumab administration in patients with breast cancer is associated with transcriptional induction of the estrogen receptor or selection of tumor clones with high expression of ESR1.

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