scholarly journals Inhibition of trans-retinoic acid-resistant human breast cancer cell growth by retinoid X receptor-selective retinoids.

1997 ◽  
Vol 17 (11) ◽  
pp. 6598-6608 ◽  
Author(s):  
Q Wu ◽  
M I Dawson ◽  
Y Zheng ◽  
P D Hobbs ◽  
A Agadir ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Retinoic Acid ◽  
Growth Inhibition ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Breast Cancer Cell Lines ◽  
Trans Retinoic Acid

All-trans-retinoic acid (trans-RA) and other retinoids exert anticancer effects through two types of retinoid receptors, the RA receptors (RARs) and retinoid X receptors (RXRs). Previous studies demonstrated that the growth-inhibitory effects of trans-RA and related retinoids are impaired in certain estrogen-independent breast cancer cell lines due to their lower levels of RAR alpha and RARbeta. In this study, we evaluated several synthetic retinoids for their ability to induce growth inhibition and apoptosis in both trans-RA-sensitive and trans-RA-resistant breast cancer cell lines. Our results demonstrate that RXR-selective retinoids, particularly in combination with RAR-selective retinoids, could significantly induce RARbeta and inhibit the growth and induce the apoptosis of trans-RA-resistant, RAR alpha-deficient MDA-MB-231 cells but had low activity against trans-RA-sensitive ZR-75-1 cells that express high levels of RAR alpha. Using gel retardation and transient transfection assays, we found that the effects of RXR-selective retinoids on MDA-MB-231 cells were most likely mediated by RXR-nur77 heterodimers that bound to the RA response element in the RARbeta promoter and activated the RARbeta promoter in response to RXR-selective retinoids. In contrast, growth inhibition by RAR-selective retinoids in trans-RA-sensitive, RAR alpha-expressing cells most probably occurred through RXR-RAR alpha heterodimers that also bound to and activated the RARbeta promoter. In MDA-MB-231 clones stably expressing RAR alpha, both RARbeta induction and growth inhibition by RXR-selective retinoids were suppressed, while the effects of RAR-selective retinoids were enhanced. Together, our results demonstrate that activation of RXR can inhibit the growth of trans-RA-resistant MDA-MB-231 breast cancer cells and suggest that low cellular RAR alpha may regulate the signaling switch from RAR-mediated to RXR-mediated growth inhibition in breast cancer cells.

Lovastatin enhances the antiproliferative effect of trastuzumab in HER2 over expressing breast cancer cells

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 2546-2546
Author(s):  
O. M. Halaweh ◽  
C. Lobocki ◽  
L. Dumasia ◽  
A. Drelichman
Keyword(s):  
Breast Cancer ◽  
Growth Inhibition ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Antiproliferative Effect ◽  
Breast Cancer Cell Lines ◽  
Human Breast

2546 Background: Trastuzumab, a recombinant humanized anti-HER2 monoclonal antibody, has been found to have potent antiproliferative effects in HER2 overexpressing human breast tumors. Lovastatin, an HMG-CoA reductase inhibitor suppresses growth, and induces apoptosis in breast cancer cells. Both agents induce a G0/G1 arrest of cell cycle progression. The purpose of this study was to evaluate the antiproliferative effect of the novel combination of lovastatin and trastuzumab in human breast cancer cell lines. Methods: Increasing doses of lovastatin (0.16-40 μM) and trastuzumab (0.039-1 μg/ml) were tested alone and in combination. Three breast carcinoma cell lines were studied: two HER2 overexpressing lines (BT474 and SKBR3) and one cell line that expresses low levels of the receptor (MCF7). Inhibition of growth was assessed after 7 days of treatment by the MTT colorimetric assay, while apoptosis was detected using an in situ DNA Fragmentation Detection kit. Results: A dose-dependent growth inhibition was demonstrated in all three cell lines tested with lovastatin, while trastuzumab was only effective in the HER2 overexpressing cells. Trastuzumab (0.06 μg/ml) inhibited cell growth by 29.3% and 40.1%, while lovastatin (2.5 μM) caused an inhibition of 19.1% and 43% in the BT474 and SKBR3 cell lines, respectively. The combination of trastuzumab and lovastatin, at these doses, significantly inhibited growth in BT474 and SKBR3 cells by 45.4% and 68.9% (P < 0.001, oneway ANOVA) compared to either agent alone. Conclusions: Lovastatin plus trastuzumab treatment led to increased growth inhibition in HER2 positive breast cancer cell lines. Further studies in an animal model are warranted. This combination may also have important clinical therapeutic implications. No significant financial relationships to disclose.

scholarly journals Antiplatelet Therapy Combined with Anastrozole Induces Features of Partial EMT in Breast Cancer Cells and Fails to Mitigate Breast-Cancer Induced Hypercoagulation

2021 ◽  
Vol 22 (8) ◽  
pp. 4153
Author(s):  
Kutlwano R. Xulu ◽  
Tanya N. Augustine
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Antiplatelet Therapy ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines

Thromboembolic complications are a leading cause of morbidity and mortality in cancer patients. Cancer patients often present with an increased risk for thrombosis including hypercoagulation, so the application of antiplatelet strategies to oncology warrants further investigation. This study investigated the effects of anastrozole and antiplatelet therapy (aspirin/clopidogrel cocktail or atopaxar) treatment on the tumour responses of luminal phenotype breast cancer cells and induced hypercoagulation. Ethical clearance was obtained (M150263). Blood was co-cultured with breast cancer cell lines (MCF7 and T47D) pre-treated with anastrozole and/or antiplatelet drugs for 24 h. Hypercoagulation was indicated by thrombin production and platelet activation (morphological and molecular). Gene expression associated with the epithelial-to-mesenchymal transition (EMT) was assessed in breast cancer cells, and secreted cytokines associated with tumour progression were evaluated. Data were analysed with the PAST3 software. Our findings showed that antiplatelet therapies (aspirin/clopidogrel cocktail and atopaxar) combined with anastrozole failed to prevent hypercoagulation and induced evidence of a partial EMT. Differences in tumour responses that modulate tumour aggression were noted between breast cancer cell lines, and this may be an important consideration in the clinical management of subphenotypes of luminal phenotype breast cancer. Further investigation is needed before this treatment modality (combined hormone and antiplatelet therapy) can be considered for managing tumour associated-thromboembolic disorder.

scholarly journals Highly expressed SLCO1B3 inhibits the occurrence and development of breast cancer and can be used as a clinical indicator of prognosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tiantian Tang ◽  
Guiying Wang ◽  
Sihua Liu ◽  
Zhaoxue Zhang ◽  
Chen Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Migration And Invasion ◽  
Breast Cancer Cell Lines

AbstractThe role of organic anion transporting polypeptide 1B3 (SLCO1B3) in breast cancer is still controversial. The clinical immunohistochemical results showed that a greater proportion of patients with negative lymph nodes, AJCC stage I, and histological grade 1 (P < 0.05) was positively correlated with stronger expression of SLCO1B3, and DFS and OS were also increased significantly in these patients (P = 0.041, P = 0.001). Further subgroup analysis showed that DFS and OS were significantly enhanced with the increased expression of SLCO1B3 in the ER positive subgroup. The cellular function assay showed that the ability of cell proliferation, migration and invasion was significantly enhanced after knockdown of SLCO1B3 expression in breast cancer cell lines. In contrast, the ability of cell proliferation, migration and invasion was significantly reduced after overexpress the SLCO1B3 in breast cancer cell lines (P < 0.05). Overexpression or knockdown of SLCO1B3 had no effect on the apoptotic ability of breast cancer cells. High level of SLCO1B3 expression can inhibit the proliferation, invasion and migration of breast cancer cells, leading to better prognosis of patients. The role of SLCO1B3 in breast cancer may be related to estrogen. SLCO1B3 will become a potential biomarker for breast cancer diagnosis and prognosis assessment.

scholarly journals MicroRNA in combination with HER2-targeting drugs reduces breast cancer cell viability in vitro

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lisa Svartdal Normann ◽  
Miriam Ragle Aure ◽  
Suvi-Katri Leivonen ◽  
Mads Haugland Haugen ◽  
Vesa Hongisto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Targeted Treatment ◽  
Breast Cancer Cell Lines ◽  
Altered Expression ◽  
Her2 Breast Cancer

AbstractHER2-positive (HER2 +) breast cancer patients that do not respond to targeted treatment have a poor prognosis. The effects of targeted treatment on endogenous microRNA (miRNA) expression levels are unclear. We report that responsive HER2 + breast cancer cell lines had a higher number of miRNAs with altered expression after treatment with trastuzumab and lapatinib compared to poorly responsive cell lines. To evaluate whether miRNAs can sensitize HER2 + cells to treatment, we performed a high-throughput screen of 1626 miRNA mimics and inhibitors in combination with trastuzumab and lapatinib in HER2 + breast cancer cells. We identified eight miRNA mimics sensitizing cells to targeted treatment, miR-101-5p, mir-518a-5p, miR-19b-2-5p, miR-1237-3p, miR-29a-3p, miR-29c-3p, miR-106a-5p, and miR-744-3p. A higher expression of miR-101-5p predicted better prognosis in patients with HER2 + breast cancer (OS: p = 0.039; BCSS: p = 0.012), supporting the tumor-suppressing role of this miRNA. In conclusion, we have identified miRNAs that sensitize HER2 + breast cancer cells to targeted therapy. This indicates the potential of combining targeted drugs with miRNAs to improve current treatments for HER2 + breast cancers.

The α2δ1 subunit of the voltage-gated calcium channel as a potential candidate for breast cancer tumor initial cells biomarker

2021 ◽  
pp. 1-11
Author(s):  
Meng Li ◽  
Wenmin Zhang ◽  
Xiaodan Yang ◽  
Guo An ◽  
Wei Zhao
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Self Renewal

BACKGROUND: The voltage-gated calcium channel subunit alpha 2 delta 1 (α2δ1) is a functional tumor initial cells (TICs) marker for some solid cancer cells. This study aimed to investigate whether α2δ1 can be used as a potential TIC marker for breast cancer cells. METHODS: α2δ1+ and α2δ1- cells were identified and sorted from the breast cancer cell lines MDA-MB-231, MDA-MB-435s and ZR-75-1 by Immunofluorescence (IF) and Fluorescent-activated cell sorting (FACS) analyses. Spheroid formation in vitro and tumorigenesis in NOD/SCID mice were assessed to determine the self-renewal and serial transplantation abilities of these cells. Using a lentivirus infection system for α2δ1 in breast cancer cell lines, we determined the mRNA levels of stemnessassociated genes by quality real-time PCR (qRT-PCR). Boyden chamber and wounding assays were further performed to detect the migration of α2δ1 overexpression cells. Bioinformatics explored the relationship of molecular classification of breast cancer and drug resistance. RESULTS: α2δ1 presents on the cytomembrane of breast cancer cells, with a positive rate of 1.5–3%. The α2δ1+ cells in breast cancer cell lines have a stronger self-renewal ability and tumor initiating properties in vitro and in vivo. Overexpressing α2δ1 successfully enhanced the sphere-forming efficiency, and upregulated the expression of stemness-associated genes, and increased cell migration. However, seldom significant was available between estrogen receptor +/- (ER+/-), progesterone receptor (PR+/-), and Her2+/-. CONCLUSIONS: Breast cancer cells positive for the α2δ1 charactered tumor initiation, and α2δ1 is a potential TIC marker for breast cancer that further promotes the migration.

Solanum nigrum Anticancer Effect Through Epigenetic Modulations in Breast Cancer Cell Lines

2020 ◽  
Vol 16 (2) ◽  
pp. 121-126
Author(s):  
Atefeh Shirkavand ◽  
Zahra N. Boroujeni ◽  
Seyed A. Aleyasin
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Methylation Status ◽  
Cancer Cell Lines ◽  
Solanum Nigrum ◽  
Breast Cancer Cell Lines

Background: DNA methylation plays an important role in the regulation of gene expression in mammalian cells and often occurs at CpG islands in the genome. It is more reversible than genetic variations and has therefore attracted much attention for the treatment of many diseases, especially cancer. In the present study, we investigated the effect of Solanum nigrum Extract (SNE) on the methylation status of the VIM and CXCR4 genes in breast cancer cell lines. Methods: The Trypan blue assay was used to study the effect of SNE at various concentrations of 0, 0.1, 1.5, 2.5, 3.5 and 5 mg/ml for 48 h on the survival of three human breast cancer cell lines MCF7, MDA-MB-468, MDA-MB-231. Methylation status of VIM and CXCR4 genes in breast cancer cell lines was assessed by Methylation-Specific PCR (MSP) method. Also, methylation changes of VIM and CXCR4 genes in breast cancer cell lines after treatment with 0.1 mg/ml of SNE for 6 days were analyzed by MSP method. To confirm the effect of SNE on methylation of VIM and CXCR4 genes, Real-Time PCR was performed. Results: The Trypan blue assay results indicated that treatment with SNE reduced cell viability in a dose-dependent manner in breast cancer cells. Our results showed that treatment of breast cancer cells with 0.1 mg/ml of SNE hypermethylated the VIM, CXCR4 genes and significantly reduced the expression levels of their mRNA (P<0.05). Conclusion: Our findings reveal for the first time the impact of SNE on the methylation of breast cancer cells.

scholarly journals Matrix Metalloproteinase 8 (Collagenase 2) Induces the Expression of Interleukins 6 and 8 in Breast Cancer Cells

2013 ◽  
Vol 288 (23) ◽  
pp. 16282-16294 ◽  
Author(s):  
Sally Thirkettle ◽  
Julie Decock ◽  
Hugh Arnold ◽  
Caroline J. Pennington ◽  
Diane M. Jaworski ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Matrix Metalloproteinase ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Breast Cancer Cell Lines

Matrix metalloproteinase 8 (MMP-8) is a tumor-suppressive protease that cleaves numerous substrates, including matrix proteins and chemokines. In particular, MMP-8 proteolytically activates IL-8 and, thereby, regulates neutrophil chemotaxis in vivo. We explored the effects of expression of either a WT or catalytically inactive (E198A) mutant version of MMP-8 in human breast cancer cell lines. Analysis of serum-free conditioned media from three breast cancer cell lines (MCF-7, SK-BR-3, and MDA-MB-231) expressing WT MMP-8 revealed elevated levels of IL-6 and IL-8. This increase was mirrored at the mRNA level and was dependent on MMP-8 catalytic activity. However, sustained expression of WT MMP-8 by breast cancer cells was non-permissive for long-term growth, as shown by reduced colony formation compared with cells expressing either control vector or E198A mutant MMP-8. In long-term culture of transfected MDA-MB-231 cells, expression of WT but not E198A mutant MMP-8 was lost, with IL-6 and IL-8 levels returning to base line. Rare clonal isolates of MDA-MB-231 cells expressing WT MMP-8 were generated, and these showed constitutively high levels of IL-6 and IL-8, although production of the interleukins was no longer dependent upon MMP-8 activity. These studies support a causal connection between MMP-8 activity and the IL-6/IL-8 network, with an acute response to MMP-8 involving induction of the proinflammatory mediators, which may in part serve to compensate for the deleterious effects of MMP-8 on breast cancer cell growth. This axis may be relevant to the recognized ability of MMP-8 to orchestrate the innate immune system in inflammation in vivo.

scholarly journals Studying the Genomic Role of Cathepsin-D in ER+ Breast Cancer

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A817-A818
Author(s):  
Elham Dianati ◽  
Emmanuelle Liaudet-coopman ◽  
Sylvie Mader
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cathepsin D ◽  
Breast Cancer Cells ◽  
Cancer Cell Lines ◽  
Proximity Ligation Assay ◽  
Breast Cancer Cell Lines

Abstract Estrogen receptor alpha (ERα), a transcription factor implicated in induction of cell growth in breast cancer, is a therapeutic target that is expressed in &gt;70% of breast tumors. The transcriptional activity of ERα is controlled by ligands and increased through its interaction with co-activators such as the p160/SRC and p300/CBP families. In an attempt to identify the ligand-specific protein complexes involved in transcriptional regulation by ERα, BioID and TurboID screens were performed in two ER+ breast cancer cell lines, T-47D and ZR-75-1. Surprisingly, Cathepsin-D (Cath-D), a lysosomal aspartyl endoproteinase that is an ER target gene, was identified in these screens. Cath-D expression is associated with a poor prognosis and increased metastasis rate in breast cancer irrespective of its catalytic activities {Glondu, 2001 #119}[i]. Cath-D is localized in part to the nucleus where it interacts with TRPS1, a repressor of GATA-mediated transcription and modulator of ERα signaling {Bach, 2015 #117}[ii]. Co-silencing Cath-D and TRPS1 suppressed cell proliferation and inhibited growth under soft agar, suggesting that they cooperate to drive tumorigenesis {Bach, 2015 #117}[ii]. We hypothesized that Cath-D plays genomic as well as non-genomic roles in breast tumor aggressiveness and may alter ERα-mediated transcription. The nuclear localization of Cath-D was confirmed by immunofluorescence using different commercialized antibodies and observed in western blots of chromatin-bound fractions in three different ERα+ breast cancer cell lines, T-47D, ZR-75 and MCF-7. Specificity of the antibodies was confirmed using siRNA-mediated suppression of Cath-D. Moreover, Cath-D was also identified in proximity to TurboID-ERα by LC-MS after chromatin fractionation. The proximity of ERα and Cath-D both in the cytoplasm and nucleus was confirmed by proximity Ligation Assay (PLA) in three ER+ cell lines. Co-immunoprecipitation assays indicated physical interaction of Cath-D with ERα in T-47D cell extracts. Further, Cath-D was detected by ChIP-qPCR on estrogen response elements (EREs) of two ERα target genes, TFF1 and GREB1 in T-47D and ZR-75 cells. These results suggest that Cath-D can interact with ERα on DNA and play genomic roles in ER+ breast cancer cells. [i] Glondu, M., et al. (2001). “A mutated cathepsin-D devoid of its catalytic activity stimulates the growth of cancer cells.” Oncogene20(47): 6920-6929. [ii] Bach, A. S., et al. (2015). “Nuclear cathepsin D enhances TRPS1 transcriptional repressor function to regulate cell cycle progression and transformation in human breast cancer cells.” Oncotarget6(29): 28084-28103.

scholarly journals Deciphering the Oncogenic Role of VPS28 Modulated by miR-491-5p in Breast Cancer Cells Using In Silico and Functional Analysis

2021 ◽  
Vol 8 ◽  
Author(s):  
Wenjie Shi ◽  
Daojun Hu ◽  
Yu Xing ◽  
Rui Zhuo ◽  
Qiufeng Lao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
In Silico ◽  
Breast Cancer Cells ◽  
Breast Cancer Cell Lines ◽  
Biological Functions ◽  
Cancer Tissues

Vacuolar protein sorting–associated protein 28 (VPS28), one of the four cytosolic proteins comprising the endosomal sorting complex required for the transport I (ESCRT-I) component, has been reported to be linked to various cancers. However, less evidence is available regarding the involvement of VPS28 in breast cancer. To this end, this study focused on exploring the function of VPS28 in breast cancer cells using the in silico analysis. VPS28 expression pattern data in breast cancer tissues were collected using the Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC) databases and analyzed to assess the association of VPS28 with breast cancer prognosis. The elevated VPS28 expression was found in breast cancer tissues and was associated with a poor prognosis (p &lt; 0.001). A higher VPS28 expression indicated a short survival duration (HR = 2.43; 95% CI: 1.44–4.1; p &lt; 0.001). The CCLE database showed that VPS28 was expressed in breast cancer cell lines. The upstream targets of VPS28 were identified using the mirDIP, starBase, and TargetScan online tools. The correlation and binding relationship between miR-491-5p and VPS28 was analyzed. VPS28 or miR-491-5p gain and loss of function experiments were performed to verify their potential effect on the biological functions of breast cancer cells. Knockdown of VPS28 was shown to suppress the biological functions and enhance the apoptosis of breast cancer cell lines. Micro RNA-491-5p, identified as a posttranscriptional regulator of VPS28, was downregulated in breast cancer tissues. In contrast to the miR-491-5p inhibitor, the miR-491-5p mimic could suppress the migration, wound healing ability, and proliferation, while accelerating apoptosis. However, co-transfection of VPS28 and miR-491-5p counteracted the effect of the miR-491-5p mimic on breast cancer cell functions. Thus, our in silico analysis demonstrates that miR-491-5p can suppress breast cancer progression by attenuating the expression of VPS28.

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