scholarly journals SUN-733 Analysis of Divergent Long Noncoding RNAs in Estrogen-Regulated Transcription

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Debra Lee ◽  
Barabara Yang ◽  
Melina Sedano ◽  
Ramesh Choudhari ◽  
Shrikanth S Gadad
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Biology ◽  
Breast Cancer Cells ◽  
Expression Patterns ◽  
Critical Role ◽  
Noncoding Rnas ◽  
Subcellular Fractionation ◽  
Long Noncoding Rnas ◽  
Intron Structure

Abstract The role of long noncoding RNAs (lncRNAs) in cancer biology are just beginning to be elucidated and recent studies have shown that they could be therapeutic targets. In a previous study, combining powerful techniques, Global Run-On sequencing (GRO-seq) and subcellular fractionation RNA-seq in breast cancer cells identified a large number of estrogen-regulated unannotated long noncoding RNAs. Analysis of gene expression data from hundreds of samples representing 13 different tissue types including both cancer and normal tissue, revealed that many lncRNAs are differentially expressed in various cancers. Furthermore, a large number of lncRNAs are divergent transcripts and show distinct expression patterns across molecular subtypes of cancer. In functional assays, knockdown of selected lncRNA, such as lncRNA67, inhibits the growth of breast cancer cells. Amplified expression of lncRNA67 in luminal-subtype of breast cancer correlates with clinical outcome. LncRNA67 has now been fully annotated (transcription start and stop site, 5’ cap, polyA tail, and exon/intron structure), and cloned. Our preliminary molecular analyses indicate that lncRNA67 plays a critical role in ER-dependent and -independent pathways. Collectively, our results suggest that lncRNAs are an integral component of cancer biology.

scholarly journals SUN-743 Understanding the Role of Pancreas and Testis Specific lncRNA86 in Estrogen-Dependent Signaling in Breast Cancer

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Enrique Ivan Ramos ◽  
Barbara Yang ◽  
Ramesh Choudhari ◽  
Laura Sanchez-Michael ◽  
Melina Sedano ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Biology ◽  
Expression Patterns ◽  
Critical Role ◽  
Rna Seq ◽  
Cellular Processes ◽  
Er Positive ◽  
Intron Structure ◽  
Cancer Phenotypes ◽  
Underlying Mechanisms

Abstract Long noncoding RNAs (lncRNAs) are emerging as key regulators of diverse cellular processes, but their roles in breast cancer biology are just beginning to be elucidated. In this study, integration of powerful techniques, RNA-seq data from subcellular fractionated RNA with GRO-seq data has yielded a comprehensive catalog of estrogen-regulated lncRNAs in MCF-7 cells. Analysis of RNA-seq data from samples representing molecular subtypes of breast cancer and normal tissue types, revealed that many lncRNAs (such as lincRNA86) show distinct expression patterns. LincRNA86 shows highest normal expression in pancreas followed by testis in normal human tissues. The hypothesis is lincRNA86 regulate estrogen-dependent signaling in breast cancer. In functional assays, knockdown of lncRNA86 inhibits the growth of ER-positive breast cancer cells. Amplified expression of lncRNA86 in breast cancer correlates with clinical outcome. LncRNA86 have now been fully annotated (transcription start and stop site, 5’ cap, polyA tail, and exon/intron structure), and cloned. We are now performing detailed molecular analyses to better understand the underlying mechanisms of action of the lncRNA. We are also currently have experiments underway to view cancer phenotypes: estrogen-dependent tumor growth. Collectively, our preliminary results suggest that lincRNA86 plays a critical role in ERα-dependent pathways.

scholarly journals Effect of SALL4 on the Proliferation, Invasion and Apoptosis of Breast Cancer Cells

2020 ◽  
Vol 19 ◽  
pp. 153303382098007
Author(s):  
Chong Liu ◽  
Fan Yao ◽  
Xiaoyun Mao ◽  
Wanming Li ◽  
Hang Chen
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Expression Patterns ◽  
Critical Role ◽  
Migration And Invasion ◽  
Breast Cancer Cell Lines ◽  
Tissue Samples ◽  
Noncancerous Tissue ◽  
Cancer Tissues

Objective: We aimed to identify the expression of Sal-like 4 (SALL4) in breast cancer tissues and to explore the role of this gene in the carcinogenesis of breast cancer cells. Methods: A total of 62 paired breast cancer and noncancerous tissue samples were obtained from patients with breast cancer. SALL4 expression patterns and their association with clinicopathological characteristics were investigated by qRT-PCR, western blotting, and immunochemistry in breast cancer tissues. After the knockdown of SALL4 by short hairpin RNAs (shRNAs), the proliferative, invasive, and apoptotic abilities of MDA-MB-435 and MDA-MB-468 cells (breast cancer cell lines) were measured by colony formation and CCK-8 assays, wound healing and transwell assays, and flow cytometry, respectively. Results: SALL4 expression was higher in breast cancer tissues than that in the paired noncancerous tissues, and increased SALL4 expression in tumor tissues was closely related to tumor size and lymphatic metastasis. Furthermore, functional experiments revealed that SALL4 knockdown inhibited the cell proliferation, induced cell cycle arrest in G0/G1phase and apoptosis, and decreased the ability of migration and invasion in breast cancer cells. Additionally, our study first demonstrated that SALL4 played a critical role in modulating the tumorigenicity of breast cancer cells via the WNT/β-catenin signaling pathway. Conclusions: Our results suggest that the expression of SALL4 is upregulated in breast cancer, and this upregulation is involved in the regulation of cell growth, invasion, and apoptosis. Hence, SALL4 may be a promising target for diagnosis and therapy in patients with breast cancer.

scholarly journals Transcriptional coregualtor NUPR1 maintains tamoxifen resistance in breast cancer cells

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Lingling Wang ◽  
Jiashen Sun ◽  
Yueyuan Yin ◽  
Yanan Sun ◽  
Jinyi Ma ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Critical Role ◽  
Endocrine Resistance ◽  
Autophagic Flux ◽  
Physical Interaction ◽  
Premature Senescence ◽  
Breast Cancers ◽  
Transcriptional Coregulator

AbstractTo support cellular homeostasis and mitigate chemotherapeutic stress, cancer cells must gain a series of adaptive intracellular processes. Here we identify that NUPR1, a tamoxifen (Tam)-induced transcriptional coregulator, is necessary for the maintenance of Tam resistance through physical interaction with ESR1 in breast cancers. Mechanistically, NUPR1 binds to the promoter regions of several genes involved in autophagy process and drug resistance such as BECN1, GREB1, RAB31, PGR, CYP1B1, and regulates their transcription. In Tam-resistant ESR1 breast cancer cells, NUPR1 depletion results in premature senescence in vitro and tumor suppression in vivo. Moreover, enforced-autophagic flux augments cytoplasmic vacuolization in NUPR1-depleted Tam resistant cells, which facilitates the transition from autophagic survival to premature senescence. Collectively, these findings suggest a critical role for NUPR1 as a transcriptional coregulator in enabling endocrine persistence of breast cancers, thus providing a vulnerable diagnostic and/or therapeutic target for endocrine resistance.

scholarly journals Learning deep features for dead and living breast cancer cell classification without staining

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Gisela Pattarone ◽  
Laura Acion ◽  
Marina Simian ◽  
Emmanuel Iarussi
Keyword(s):  
Breast Cancer ◽  
Machine Learning ◽  
Drug Treatment ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Biology ◽  
Breast Cancer Cells ◽  
Bright Field ◽  
Cell Classification

AbstractAutomated cell classification in cancer biology is a challenging topic in computer vision and machine learning research. Breast cancer is the most common malignancy in women that usually involves phenotypically diverse populations of breast cancer cells and an heterogeneous stroma. In recent years, automated microscopy technologies are allowing the study of live cells over extended periods of time, simplifying the task of compiling large image databases. For instance, there have been several studies oriented towards building machine learning systems capable of automatically classifying images of different cell types (i.e. motor neurons, stem cells). In this work we were interested in classifying breast cancer cells as live or dead, based on a set of automatically retrieved morphological characteristics using image processing techniques. Our hypothesis is that live-dead classification can be performed without any staining and using only bright-field images as input. We tackled this problem using the JIMT-1 breast cancer cell line that grows as an adherent monolayer. First, a vast image set composed by JIMT-1 human breast cancer cells that had been exposed to a chemotherapeutic drug treatment (doxorubicin and paclitaxel) or vehicle control was compiled. Next, several classifiers were trained based on well-known convolutional neural networks (CNN) backbones to perform supervised classification using labels obtained from fluorescence microscopy images associated with each bright-field image. Model performances were evaluated and compared on a large number of bright-field images. The best model reached an AUC = 0.941 for classifying breast cancer cells without treatment. Furthermore, it reached AUC = 0.978 when classifying breast cancer cells under drug treatment. Our results highlight the potential of machine learning and computational image analysis to build new diagnosis tools that benefit the biomedical field by reducing cost, time, and stimulating work reproducibility. More importantly, we analyzed the way our classifiers clusterize bright-field images in the learned high-dimensional embedding and linked these groups to salient visual characteristics in live-dead cell biology observed by trained experts.

SDF-1α regulation in breast cancer cells contacting bone marrow stroma is critical for normal hematopoiesis

Blood ◽  
2006 ◽  
Vol 108 (10) ◽  
pp. 3245-3252 ◽  
Author(s):  
Anabella L. Moharita ◽  
Marcelo Taborga ◽  
Kelly E. Corcoran ◽  
Margarette Bryan ◽  
Prem S. Patel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Cancer Cells ◽  
Connexin 43 ◽  
Breast Cancer Cells ◽  
Critical Role ◽  
Contact Inhibition ◽  
Enzyme Linked Immunosorbent Assay ◽  
Hematopoietic Regulation

Abstract Breast cancer cells (BCCs) show preference for the bone marrow (BM). An animal model showed 2 populations of BCCs in the BM with regard to their cycling states. An in vitro model of early BC entry into BM showed normal hematopoiesis. Here, we show a critical role for BCC-derived SDF-1α in hematopoietic regulation. The studies used a coculture of BM stroma and BCCs (cell lines and stage II BCCs). Northern blots and enzyme-linked immunosorbent assay (ELISA) showed gradual decreases in SDF-1α production in BCCs as they contact BM stroma, indicating partial microenvironmental effects caused by stroma on the BCCs. SDF-1 knock-down BCCs and increased exogenous SDF-1α prevented contact inhibition between BCCs and BM stroma. Contact inhibition was restored with low SDF-1α levels. Long-term culture-initiating assays with CD34+/CD38–/Lin– showed normal hematopoiesis provided that SDF-1α levels were reduced in BCCs. Gap junctions (connexin-43 [CX-43]) were formed between BCCs and BM stroma, with concomitant interaction between CD34+/CD38–/Lin– and BM stroma but not with the neighboring BCCs. In summary, SDF-1α levels are reduced in BCCs that contact BM stroma. The low levels of SDF-1α in BCCs regulate interactions between BM stroma and hematopoietic progenitors, consequently facilitating normal hematopoiesis.

Cxcl10 chemokine induces migration of ING4-deficient breast cancer cells via a novel crosstalk mechanism between the Cxcr3 and Egfr receptors

2021 ◽  
Author(s):  
Emily Tsutsumi ◽  
Jeremiah Stricklin ◽  
Emily A. Peterson ◽  
Joyce A. Schroeder ◽  
Suwon Kim
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Critical Role ◽  
Disease Free Survival ◽  
Intact Cells ◽  
Free Survival ◽  
Egfr Receptors

The chemokine Cxcl10 has been associated with poor prognosis in breast cancer, but the mechanism is not well understood. Our previous study have shown that CXCL10 was repressed by the ING4 tumor suppressor, suggesting a potential inverse functional relationship. We thus investigated a role for Cxcl10 in the context of ING4 deficiencies in breast cancer. We first analyzed public gene expression datasets and found that patients with CXCL10 -high/ ING4 -low expressing tumors had significantly reduced disease-free survival in breast cancer. In vitro , Cxcl10 induced migration of ING4 -deleted breast cancer cells, but not of ING4 -intact cells. Using inhibitors, we found that Cxcl10-induced migration of ING4 -deleted cells required Cxcr3, Egfr, and the Gβγ subunits downstream of Cxcr3, but not Gαi. Immunofluorescent imaging showed that Cxcl10 induced early transient colocalization between Cxcr3 and Egfr in both ING4 -intact and ING4 -deleted cells, which recurred only in ING4 -deleted cells. A peptide agent that binds to the internal juxtamembrane domain of Egfr inhibited Cxcr3/Egfr colocalization and cell migration. Taken together, these results presented a novel mechanism of Cxcl10 that elicits migration of ING4 -deleted cells, in part by inducing a physical or proximal association between Cxcr3 and Egfr and signaling downstream via Gβγ. These results further indicated that ING4 plays a critical role in the regulation of Cxcl10 signaling that enables breast cancer progression.

scholarly journals MiR-142-5p Acts as a Significant Regulator Through Promoting Proliferation, Invasion, and Migration in Breast Cancer Modulated by Targeting SORBS1

2019 ◽  
Vol 18 ◽  
pp. 153303381989226 ◽  
Author(s):  
Weixuan Yu ◽  
Dongwei Li ◽  
Yunda Zhang ◽  
Cheukfai Li ◽  
Chuanzhao Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Expression Patterns ◽  
Sh3 Domain ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Invasion And Migration ◽  
And Migration ◽  
Low Expression

Background: Numerous researches have demonstrated that miR-142-5p plays significant roles in several cancers, although the functional characteristic of miR-142-5p in breast cancer has not been determined. This study is designed to explore the biological significance of miR-142-5p in breast cancer clinical implication and mechanism of action. Methods: The differential expression patterns of miR-142-5p and Sorbin and SH3 domain-containing protein 1 and correlations between them and clinical significances were analyzed based on data from database. The expression levels of miR-142-5p in breast cancer cells were detected using quantitative real-time polymerase chain reaction. Cell counting kit-8, transwell, and wound healing assays were used to explore the potential functions of miR-142-5p in breast cancer cells. In addition, bioinformatics prediction analysis and luciferase reporter assay were utilized to predict and identify the potential target gene of miR-142-5p. A rescue experiment was conducted by transfecting miR-142-5p inhibitors and si-Sorbin and SH3 domain-containing protein 1 into cells to explore miR-142-5p/Sorbin and SH3 domain-containing protein 1 pairs on breast cancer cells behaviors. Results: The analysis results showed that miR-142-5p was highly expressed in patients with breast cancer, while Sorbin and SH3 domain-containing protein 1 presented a trend of low expression. The clinical significances analysis suggested that the overexpression of miR-142-5p is closely correlated with metastasis, while low expression of Sorbin and SH3 domain-containing protein 1 is correlated with clinicopathological characteristics and poor overall survival in patients with breast cancer. In vitro exploration, the expression of miR-142-5p was upregulated in breast cancer cells and inhibition of miR-142-5p expression significantly reduced the proliferation, invasion, and migration of breast cancer cells. Through rescue experiments, breast cancer cells proliferation, invasion, and migration reduction induced by silencing of miR-142-5p were reversed via knockdown Sorbin and SH3 domain-containing protein 1. Conclusion: Our findings insinuate that miR-142-5p functions as a positive regulator of promoting breast cancer cells biological behaviors and clinical metastasis, possibly regulated by targeting Sorbin and SH3 domain-containing protein 1, thus providing valuable information in the development of preventive or even therapeutic strategies for utilizing miR-142-5p as a promising target.

scholarly journals Aberrant ALOX5 Activation Correlates with HER2 Status and Mediates Breast Cancer Biological Activities through Multiple Mechanisms

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Xiao Zhou ◽  
Yi Jiang ◽  
Qiuyun Li ◽  
Zhen Huang ◽  
Huawei Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Biological Activities ◽  
Critical Role ◽  
Her2 Overexpression ◽  
Her2 Positive ◽  
Mesenchymal Transition ◽  
And Migration ◽  
Expression And Activity

Arachidonate lipoxygenases (ALOX) have been implicated in playing a critical role in tumorigenesis, development, and metastasis. We previously reported that ALOX12 is involved in breast cancer chemoresistance. In this study, we demonstrate that the ALOX5 activation correlates with the HER2 expression and mediates breast cancer growth and migration. We found that the ALOX5 expression and activity were upregulated in breast cancer patients, particularly in those tissues with HER2-positive. ALOX5 upregulation was also observed in HER2-positive breast cancer cells. In contrast, HER2 inhibition led to decreased expression and activity of ALOX5 but not ALOX5AP, suggesting that HER2 specifically regulates the ALOX5 expression and activity in breast cancer cells. We further demonstrated that ALOX5 is important for breast cancer biological activities with the predominant roles in growth and migration, likely through RhoA, focal adhesion, and PI3K/Akt/mTOR signaling but not epithelial mesenchymal transition (EMT). Our work is the first to report a correlation between the ALOX5 activity and HER2 overexpression in breast cancer. Our findings also highlight the therapeutic value of inhibiting ALOX5 in breast cancer, particularly those patients with the HER2 overexpression.

scholarly journals S100A4 released from highly bone-metastatic breast cancer cells plays a critical role in osteolysis

Bone Research ◽  
2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Haemin Kim ◽  
Bongjun Kim ◽  
Sang Il Kim ◽  
Hyung Joon Kim ◽  
Brian Y. Ryu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Metastasis ◽  
Bone Loss ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cancer Metastasis ◽  
Critical Role ◽  
Bone Destruction ◽  
Metastatic Breast ◽  
Breast Cancer Patients

Abstract Bone destruction induced by breast cancer metastasis causes severe complications, including death, in breast cancer patients. Communication between cancer cells and skeletal cells in metastatic bone microenvironments is a principal element that drives tumor progression and osteolysis. Tumor-derived factors play fundamental roles in this form of communication. To identify soluble factors released from cancer cells in bone metastasis, we established a highly bone-metastatic subline of MDA-MB-231 breast cancer cells. This subline (mtMDA) showed a markedly elevated ability to secrete S100A4 protein, which directly stimulated osteoclast formation via surface receptor RAGE. Recombinant S100A4 stimulated osteoclastogenesis in vitro and bone loss in vivo. Conditioned medium from mtMDA cells in which S100A4 was knocked down had a reduced ability to stimulate osteoclasts. Furthermore, the S100A4 knockdown cells elicited less bone destruction in mice than the control knockdown cells. In addition, administration of an anti-S100A4 monoclonal antibody (mAb) that we developed attenuated the stimulation of osteoclastogenesis and bone loss by mtMDA in mice. Taken together, our results suggest that S100A4 released from breast cancer cells is an important player in the osteolysis caused by breast cancer bone metastasis.

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