scholarly journals A transcriptional enhancer required for the differential expression of the human estrogen receptor in breast cancers.

1997 ◽  
Vol 17 (3) ◽  
pp. 1274-1280 ◽  
Author(s):  
Z Tang ◽  
I Treilleux ◽  
M Brown
Keyword(s):  
Estrogen Receptor ◽  
Cell Lines ◽  
Protein Complexes ◽  
Proximal Promoter ◽  
Breast Cancer Cell Lines ◽  
Breast Cancers ◽  
Transcriptional Enhancer ◽  
Enhancer Activity ◽  
Cis Acting ◽  
Er Expression

Breast cancers lacking estrogen receptor (ER) expression have an adverse prognosis and fail to respond to endocrine therapy. We have identified a transcriptional enhancer in the human ER gene which is differentially active in ER-positive (ER+) and ER-negative (ER-) human breast cancer cell lines. Enhancer function was mapped to a 35-bp element located from -3778 to -3744 upstream of the major human ER mRNA start site, which we have termed ER-EH0 (for estrogen receptor enhancer). Gel retardation assays with ER+ and ER- cell lines identified multiple DNA-protein complexes which specifically form on this enhancer. One of these complexes could be supershifted by anti-Jun or anti-Fos antibodies, identifying it as an AP-1-containing complex. Methylation interference assays suggest binding of factors to both the AP-1 site and adjacent base pairs. Enhancer activity requires both the AP-1 site and these adjacent sequences. Mutations introduced into ER-EH0 and the recently described proximal promoter element ERF-1 in the context of the full-length promoter confirm ER-EH0 as the dominant cis-acting element involved in differential ER expression.

scholarly journals MiR-195 and Its Target SEMA6D Regulate Chemoresponse in Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 5979
Author(s):  
Diana E. Baxter ◽  
Lisa M. Allinson ◽  
Waleed S. Al Amri ◽  
James A. Poulter ◽  
Arindam Pramanik ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cell Lines ◽  
Target Genes ◽  
Breast Cancer Cell Lines ◽  
Molecular Characteristics ◽  
Chemotherapy Response ◽  
Breast Cancers ◽  
Microrna Target ◽  
Estrogen Receptor Positive

Background: poor prognosis primary breast cancers are typically treated with cytotoxic chemotherapy. However, recurrences remain relatively common even after this aggressive therapy. Comparison of matched tumours pre- and post-chemotherapy can allow identification of molecular characteristics of therapy resistance and thereby potentially aid discovery of novel predictive markers or targets for chemosensitisation. Through this comparison, we aimed to identify microRNAs associated with chemoresistance, define microRNA target genes, and assess targets as predictors of chemotherapy response. Methods: cancer cells were laser microdissected from matched breast cancer tissues pre- and post-chemotherapy from estrogen receptor positive/HER2 negative breast cancers showing partial responses to epirubicin/cyclophosphamide chemotherapy (n = 5). MicroRNA expression was profiled using qPCR arrays. MicroRNA/mRNA expression was manipulated in estrogen receptor positive/HER2 negative breast cancer cell lines (MCF7 and MDA-MB-175 cells) with mimics, inhibitors or siRNAs, and chemoresponse was assessed using MTT and colony forming survival assays. MicroRNA targets were identified by RNA-sequencing of microRNA mimic pull-downs, and comparison of these with mRNAs containing predicted microRNA binding sites. Survival correlations were tested using the METABRIC expression dataset (n = 1979). Results: miR-195 and miR-26b were consistently up-regulated after therapy, and changes in their expression in cell lines caused significant differences in chemotherapy sensitivity, in accordance with up-regulation driving resistance. SEMA6D was defined and confirmed as a target of the microRNAs. Reduced SEMA6D expression was significantly associated with chemoresistance, in accordance with SEMA6D being a down-stream effector of the microRNAs. Finally, low SEMA6D expression in breast cancers was significantly associated with poor survival after chemotherapy, but not after other therapies. Conclusions: microRNAs and their targets influence chemoresponse, allowing the identification of SEMA6D as a predictive marker for chemotherapy response that could be used to direct therapy or as a target in chemosensitisation strategies.

scholarly journals LPTO-06. A NOVEL BRAIN-PERMEANT CHEMOTHERAPEUTIC AGENT FOR THE TREATMENT OF BREAST CANCER LEPTOMENINGEAL METASTASIS

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i7-i7
Author(s):  
Jiaojiao Deng ◽  
Sophia Chernikova ◽  
Wolf-Nicolas Fischer ◽  
Kerry Koller ◽  
Bernd Jandeleit ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Tumors ◽  
Cell Lines ◽  
Chemotherapeutic Agent ◽  
Leptomeningeal Metastasis ◽  
Breast Cancer Cell Lines ◽  
Normal Brain ◽  
Breast Cancers

Abstract Leptomeningeal metastasis (LM), a spread of cancer to the cerebrospinal fluid and meninges, is universally and rapidly fatal due to poor detection and no effective treatment. Breast cancers account for a majority of LMs from solid tumors, with triple-negative breast cancers (TNBCs) having the highest propensity to metastasize to LM. The treatment of LM is challenged by poor drug penetration into CNS and high neurotoxicity. Therefore, there is an urgent need for new modalities and targeted therapies able to overcome the limitations of current treatment options. Quadriga has discovered a novel, brain-permeant chemotherapeutic agent that is currently in development as a potential treatment for glioblastoma (GBM). The compound is active in suppressing the growth of GBM tumor cell lines implanted into the brain. Radiolabel distribution studies have shown significant tumor accumulation in intracranial brain tumors while sparing the adjacent normal brain tissue. Recently, we have demonstrated dose-dependent in vitro and in vivo anti-tumor activity with various breast cancer cell lines including the human TNBC cell line MDA-MB-231. To evaluate the in vivo antitumor activity of the compound on LM, we used the mouse model of LM based on the internal carotid injection of luciferase-expressing MDA-MB-231-BR3 cells. Once the bioluminescence signal intensity from the metastatic spread reached (0.2 - 0.5) x 106 photons/sec, mice were dosed i.p. twice a week with either 4 or 8 mg/kg for nine weeks. Tumor growth was monitored by bioluminescence. The compound was well tolerated and caused a significant delay in metastatic growth resulting in significant extension of survival. Tumors regressed completely in ~ 28 % of treated animals. Given that current treatments for LM are palliative with only few studies reporting a survival benefit, Quadriga’s new agent could be effective as a therapeutic for both primary and metastatic brain tumors such as LM. REF: https://onlinelibrary.wiley.com/doi/full/10.1002/pro6.43

scholarly journals Extracellular Calcium-Sensing Receptor Expression and Its Potential Role in Regulating Parathyroid Hormone-Related Peptide Secretion in Human Breast Cancer Cell Lines*

Endocrinology ◽  
2000 ◽  
Vol 141 (12) ◽  
pp. 4357-4364 ◽  
Author(s):  
Jennifer L. Sanders ◽  
Naibedya Chattopadhyay ◽  
Olga Kifor ◽  
Toru Yamaguchi ◽  
Robert R. Butters ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Human Breast Cancer ◽  
Cancer Cell Lines ◽  
Human Breast Cancer Cell ◽  
Breast Cancer Cell Lines ◽  
Breast Cancers ◽  
Human Breast

Abstract Metastasis of breast cancer to bone occurs with advanced disease and produces substantial morbidity. Secretion of PTH-related peptide (PTHrP) from breast cancer cells is thought to play a key role in osteolytic metastases and is increased by transforming growth factor-β (TGFβ), which is released from resorbed bone. Elevated extracellular calcium (Cao2+) also stimulates PTHrP secretion from various normal and malignant cells, an action that could potentially be mediated by the Cao2+-sensing receptor (CaR) originally cloned from the parathyroid gland. Indeed, we previously showed that both normal breast ductal epithelial cells and primary breast cancers express the CaR. In this study we investigated whether the MCF-7 and MDA-MB-231 human breast cancer cell lines express the CaR and whether CaR agonists modulate PTHrP secretion. Northern blot analysis and RT-PCR revealed bona fide CaR transcripts, and immunocytochemistry and Western analysis with a specific anti-CaR antiserum demonstrated CaR protein expression in both breast cancer cell lines. Furthermore, elevated Cao2+ and the polycationic CaR agonists, neomycin and spermine, stimulated PTHrP secretion dose dependently, with maximal, 2.1- to 2.3-fold stimulation. In addition, pretreatment of MDA-MB-231 cells overnight with TGFβ1 (0.2, 1, or 5 ng/ml) augmented both basal and high Cao2+-stimulated PTHrP secretion. Thus, in PTHrP-secreting breast cancers metastatic to bone, the CaR could potentially participate in a vicious cycle in which PTHrP-induced bone resorption raises the levels of Cao2+ and TGFβ within the bony microenvironment, which then act in concert to evoke further PTHrP release and worsening osteolysis.

scholarly journals RUNX3 Epigenetic Inactivation Is Associated With Estrogen Receptor Positive Breast Cancer

2018 ◽  
Vol 66 (10) ◽  
pp. 709-721 ◽  
Author(s):  
Hui Liu ◽  
Zhantao Yan ◽  
Qianqian Yin ◽  
Kai Cao ◽  
Yu Wei ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cell Lines ◽  
Methylation Status ◽  
Gene Promoter ◽  
Migration And Invasion ◽  
Breast Cancer Cell Lines ◽  
Cancer Tissue ◽  
Er Positive ◽  
Runx3 Gene

The role of Runt-related transcription factor 3 ( RUNX3) gene in breast cancer remains not fully understood. We studied the correlation between RUNX3 gene promoter methylation and estrogen receptor (ER) expression status in breast cancer. Three breast cancer cell lines and 113 formalin-fixed, paraffin-embedded breast cancer tissue samples were analyzed for RUNX3 expression. Methylation-specific polymerase chain reaction was used to analyze RUNX3 methylation on the samples. Migration and invasion ability were evaluated in MCF7 cell line (RUNX3 methylated) treated with methylation inhibitor 5-Aza-2′-deoxycytidine (5-Aza-CdR) to study the effect of RUNX3 methylation status. Our data showed that the expression of RUNX3 was high in MCF10A but not in MCF7 and SKBR3 cell lines, while the RUNX3 promoter showed hypermethylation in MCF7 but not in MCF10A and SKBR3. In tissues samples, Immunohistochemical (IHC) expression of RUNX3 protein was higher in ER-negative samples than in ER-positive cases, and it was negatively correlated with the methylation status of the RUNX3 gene promoter. Proliferation, migration, and invasion of MCF7 were suppressed when 5-Aza-CdR treated. Also, the hypermethylation status of RUNX3 gene promoter was reversed and RUNX3 expression was increased. In summary, our data suggest that hypermethylation of the RUNX3 gene promoter may play an important role in ER-positive breast tumor progression.

scholarly journals Selective Effects of Thioridazine on Self-Renewal of Basal-Like Breast Cancer Cells

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Matthew Tegowski ◽  
Cheng Fan ◽  
Albert S. Baldwin
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Cell Types ◽  
Breast Cancer Cell Lines ◽  
Breast Cancers ◽  
Self Renewal ◽  
Basal Like Breast Cancer

AbstractSeveral recent publications demonstrated that DRD2-targeting antipsychotics such as thioridazine induce proliferation arrest and apoptosis in diverse cancer cell types including those derived from brain, lung, colon, and breast. While most studies show that 10–20 µM thioridazine leads to reduced proliferation or increased apoptosis, here we show that lower doses of thioridazine (1–2 µM) target the self-renewal of basal-like breast cancer cells, but not breast cancer cells of other subtypes. We also show that all breast cancer cell lines tested express DRD2 mRNA and protein, regardless of thioridazine sensitivity. Further, DRD2 stimulation with quinpirole, a DRD2 agonist, promotes self-renewal, even in cell lines in which thioridazine does not inhibit self-renewal. This suggests that DRD2 is capable of promoting self-renewal in these cell lines, but that it is not active. Further, we show that dopamine can be detected in human and mouse breast tumor samples. This observation suggests that dopamine receptors may be activated in breast cancers, and is the first time to our knowledge that dopamine has been directly detected in human breast tumors, which could inform future investigation into DRD2 as a therapeutic target for breast cancer.

scholarly journals Molecular and chemical characterization by Fourier transform infrared spectroscopy of human breast cancer cells with estrogen receptor expressed and not expressed

2010 ◽  
Vol 24 (5) ◽  
pp. 501-510 ◽  
Author(s):  
Leila Büttner Mostaço-Guidolin ◽  
Luciana Sayuri Murakami ◽  
Marina Ribeiro Batistuti ◽  
Auro Nomizo ◽  
Luciano Bachmann
Keyword(s):  
Breast Cancer ◽  
Fatty Acids ◽  
Estrogen Receptor ◽  
Cell Lines ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Chemical Characterization ◽  
Breast Cancer Cell Lines ◽  
Human Breast ◽  
Mcf 7

The present study was designed to identify and compare the infrared absorption spectra of two human breast cancer cell lines: MCF-7 (estrogen receptor expressed, ER+) and SKBr3 (estrogen receptor non-expressed, ER–). Comparison between SKBr3 and MCF-7 cells revealed differences in the following absorption band areas: 1087 cm–1(DNA), 1397 cm–1(CH3), 1543 cm–1(amide II), 1651 cm–1(amide I), 2924 cm–1(fatty acids). Additionally, peak shifts were observed at 1122 cm–1(RNA), 1397 cm–1(CH3), 1651 cm–1(amide I), 2851 cm–1(fatty acids) and 2962 cm–1(fatty acids). An analysis of the ratio between band areas was conducted, in order to obtain an index that could effectively distinguish between these two cell lines. The following ratios were found: 1650 cm–1/1540 cm–1, 1650 cm–1/1740 cm–1, 1650 cm–1/1084 cm–1and 1120 cm–1/1084 cm–1. This work demonstrates that it is possible to distinguish between MCF-7 and SKBr3 cells through differences in their FTIR spectra. This work enables distinction between two cell lines from the same breast cancer.

Sign in / Sign up

Export Citation Format

Share Document