scholarly journals Corrigendum: Tanshinone II A improves the chemosensitivity of breast cancer cells to doxorubicin by inhibiting β‐catenin nuclear translocation

2021 ◽  
Vol 35 (4) ◽  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Nuclear Translocation ◽  
Tanshinone Ii A

scholarly journals ROCK inhibition with Fasudil induces beta-catenin nuclear translocation and inhibits cell migration of MDA-MB 231 human breast cancer cells

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Fabiana Sélos Guerra ◽  
Ramon Guerra de Oliveira ◽  
Carlos Alberto Manssour Fraga ◽  
Claudia dos Santos Mermelstein ◽  
Patricia Dias Fernandes
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Nuclear Translocation ◽  
Beta Catenin ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Rock Inhibition

scholarly journals Nuclear ErbB2 represses DEPTOR transcription to inhibit autophagy in breast cancer cells

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Yanli Bi ◽  
Longyuan Gong ◽  
Pengyuan Liu ◽  
Xiufang Xiong ◽  
Yongchao Zhao
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Transcriptional Repression ◽  
Breast Cancer Cells ◽  
Kinase Activity ◽  
Nuclear Translocation ◽  
Extracellular Signals ◽  
Consensus Binding Sequence ◽  
Binding Sequence

AbstractErbB2, a classical receptor tyrosine kinase, is frequently overexpressed in breast cancer cells. Although the role of ErbB2 in the transmission of extracellular signals to intracellular matrix has been widely studied, the functions of nuclear ErbB2 remain largely elusive. Here, we report a novel function of nuclear ErbB2 in repressing the transcription of DEPTOR, a direct inhibitor of mTOR. Nuclear ErbB2 directly binds to the consensus binding sequence in the DEPTOR promoter to repress its transcription. The kinase activity of ErbB2 is required for its nuclear translocation and transcriptional repression of DEPTOR. Moreover, the repressed DEPTOR by nuclear ErbB2 inhibits the induction of autophagy by activating mTORC1. Thus, our study reveals a novel mechanism for autophagy regulation by functional ErbB2, which translocates to the nucleus and acts as a transcriptional regulator to suppress DEPTOR transcription, leading to activation of the PI3K/AKT/mTOR pathway to inhibit autophagy.

scholarly journals Whole-cell uptake and nuclear localization of 1,25-dihydroxycholecalciferol by breast cancer cells (T47 D) in culture

1981 ◽  
Vol 200 (2) ◽  
pp. 315-320 ◽  
Author(s):  
Elizabeth Sher ◽  
John A. Eisman ◽  
Jane M. Moseley ◽  
T. John Martin
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Binding Sites ◽  
Breast Cancer Cells ◽  
Nuclear Translocation ◽  
Vitamin D Metabolites ◽  
Intact Cells ◽  
Cells In Culture

Specific high-affinity receptors for 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] have been described recently in broken-cell preparations of several cultured human breast cancer cell lines including the T47 D line. It was necessary to determine whether intact breast cancer cells in culture would bind 1,25-(OH)2D3 specifically and whether the next step in the proposed scheme of action, i.e. nuclear translocation, occurred. The following results were obtained. (1) Specific uptake of 1,25-(OH)2D3 by T47 D cells occurs in intact cells in culture. (2) The rate of uptake is proportional to medium 1,25-(OH)2D3 concentration but is slow compared with that of other steroid hormones, e.g., oestradiol, under identical conditions. Even at 0.5nm-1,25-(OH)2D3 in the medium, at least 4h are required to reach maximum compared with less than 1h for oestradiol binding. (3) Estimation of binding characteristics by Scatchard analysis indicates a single class of binding sites with Kd of 68pm and 11800 binding sites/cell, which are similar results to those obtained with broken-cell preparations. (4) Inclusion of various vitamin D metabolites in the incubation medium decreased specific binding of 1,25-(OH)2D3 by the intact cells in a manner identical with their effects in the broken-cell preparation and with potencies similar to their potency on Ca2+ transport and bone resorption in vivo. Order of potency was 1,25-(OH)2D3>(24R)-1,24,25-trihydroxycholecalciferol »25-hydroxycholecalciferol>(25R)-24,25-dihydroxycholecalciferol »(25R)-25,26-dihydroxycholecalciferol. (5) In the 1,25-(OH)2D3-depleted state, 80% of the 1,25(OH)2D3 receptor is found in the cytosol fraction of the cells even when the subcellular fractionation is performed under low-salt conditions. By contrast after incubation with [3H]1,25-(OH)2D3, 59% of the specific 1,25-(OH)2D3 binding is found in the partially purified nuclei fraction. These data indicate that nuclear translocation of the receptor–hormone complex takes place in the intact T47 D cell. The results also support the hypothesis that the 1,25-(OH)2D3 receptor is functional in this cultured breast cancer cell line, which may provide a useful model for further study of the early biochemical events in 1,25-(OH)2D3 action.

scholarly journals HDAC5-mediated deacetylation and nuclear localisation of SOX9 is critical for tamoxifen resistance in breast cancer

2019 ◽  
Vol 121 (12) ◽  
pp. 1039-1049 ◽  
Author(s):  
Yue Xue ◽  
Wenwen Lian ◽  
Jiaqi Zhi ◽  
Wenjuan Yang ◽  
Qianjin Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Transcription Factor ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Nuclear Translocation ◽  
Tamoxifen Resistance ◽  
Nuclear Localisation ◽  
Tamoxifen Resistant ◽  
Factor C ◽  
Positive Breast Cancer

Abstract Background Tamoxifen resistance remains a significant clinical challenge for the therapy of ER-positive breast cancer. It has been reported that the upregulation of transcription factor SOX9 in ER+ recurrent cancer is sufficient for tamoxifen resistance. However, the mechanisms underlying the regulation of SOX9 remain largely unknown. Methods The acetylation level of SOX9 was detected by immunoprecipitation and western blotting. The expressions of HDACs and SIRTs were evaluated by qRT-PCR. Cell growth was measured by performing MTT assay. ALDH-positive breast cancer stem cells were evaluated by flow cytometry. Interaction between HDAC5 and SOX9 was determined by immunoprecipitation assay. Results Deacetylation is required for SOX9 nuclear translocation in tamoxifen-resistant breast cancer cells. Furthermore, HDAC5 is the key deacetylase responsible for SOX9 deacetylation and subsequent nuclear translocation. In addition, the transcription factor C-MYC directly promotes the expression of HDAC5 in tamoxifen resistant breast cancer cells. For clinical relevance, high SOX9 and HDAC5 expression are associated with lower survival rates in breast cancer patients treated with tamoxifen. Conclusions This study reveals that HDAC5 regulated by C-MYC is essential for SOX9 deacetylation and nuclear localisation, which is critical for tamoxifen resistance. These results indicate a potential therapy strategy for ER+ breast cancer by targeting C-MYC/HDAC5/SOX9 axis.

scholarly journals SAT-124 Optimization of Experimental Conditions for Mimicking Hypoxia in Cultured Breast Cancer Cells by Using Cobalt(II) Chloride (CoCl2)

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Karin Chen ◽  
Leo Satlof ◽  
Udithi Kothapalli ◽  
Noah Ziluck ◽  
Maribel Lema ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Apoptosis ◽  
Breast Cancer Cells ◽  
Nuclear Translocation ◽  
Breast Cancer Cell Lines ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Experimental Conditions

Abstract Hypoxia is a common phenomenon in solid tumor development caused by a decrease in either oxygen concentration or oxygen pressure as a result of rapid tumor cell growth. Hypoxia is characterized by stabilization of the alpha subunit of the hypoxia-inducible factor (HIF-1α) and its nuclear translocation and heterodimerization with HIF-1β. Activation of this signaling pathway involves multiple downstream effectors including carbonic anhydrase 9 (CA9, s. CAIX). A reliable method to mimic hypoxia utilizes cobalt(II) chloride (CoCl2), which directly induces the expression of HIF-1α. The aim of this study was to optimize the experimental conditions for CoCl2 treatment of breast cancer cells in vitro using three human breast cancer cell lines (MDA-MB-231, T-47D, and MCF-7 cells). We performed time- and concentration-response experiments, using various concentrations of CoCl2 (50, 100, 200, and 300 μM) for 24 and 48 hours, and measured the expression of HIF-1α and CA9 by qRT-PCR and Western blot analyses. Results demonstrated that CoCl2 downregulated HIF-1α mRNA levels but upregulated CA9 mRNA levels in a concentration- and time-dependent manner. Concomitantly, CoCl2 treatment resulted in a significant induction of HIF-1α protein levels. We further investigated the effect of the CoCl2 concentrations listed above on cell apoptosis using an in situ apoptosis detection kit. The results demonstrated that concentrations of CoCl2 up to 100 μM had no significant effect on cell apoptosis.

Effect of MDV3100, an androgen receptor signaling inhibitor, on tumor growth of estrogen and androgen receptor-positive (ER+/AR+) breast cancer xenografts.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 564-564
Author(s):  
Anthony D. Elias ◽  
Dawn R. Cochrane ◽  
Britta M. Jacobsen ◽  
Diana M. Cittelly ◽  
Erin N. Howe ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Androgen Receptor ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Cell Lines ◽  
Breast Cancer Cells ◽  
Nuclear Translocation ◽  
Breast Cancer Cell Lines ◽  
Receptor Signaling ◽  
Androgen Receptor Signaling

564 Background: The androgen receptor (AR) is detected by immunohistochemistry in approximately 75% of all invasive breast cancer; with ~88% of ER+ tumors expressing AR. Potent inhibition of AR activity could be a therapeutic strategy in ER+/AR+ breast cancer. MDV3100 is an androgen receptor signaling inhibitor (ARSI), which inhibits AR activity via three mechanisms: inhibition of androgen binding to AR, inhibition of AR nuclear translocation, and inhibition of nuclear AR-DNA binding. MDV3100 has demonstrated an overall survival benefit in men with post-docetaxel prostate cancer. Methods: Two ER+/AR+ breast cancer cell lines, MCF7 and BCK4 (recently derived from a pleurocentesis), were used to assess the proliferative effect of dihydrotestosterone (DHT) and estradiol (E2). The efficacy of MDV3100 at blocking DHT-mediated proliferation was compared to bicalutamide in ER+/AR+ breast cancer cells. MCF7 xenograft studies were performed to determine if MDV3100 can affect DHT or E2 mediated proliferation in vivo. Results: Both bicalutamide and MDV3100 inhibited DHT-mediated proliferation of ER+/AR+ cell lines. Although MDV3100 binds AR very effectively and does not bind ER, it also uniquely inhibited E2-mediated proliferation, while bicalutamide slightly enhanced E2 mediated proliferation. Results presented here demonstrate that MDV3100 inhibited E2-stimulated tumor growth of MCF7 mammary xenografts as effectively as tamoxifen. Conclusions: MDV3100 blocked both DHT- and E2-mediated growth of breast cancer cells, whereas bicalutamide enhanced E2-mediated proliferation. MDV3100 may have unique therapeutic utility in patients with AR+ breast cancer, regardless of ER status. Funding: DOD Breast Cancer Program Idea Award BC074403, Avon Foundation for Women, and University of Colorado Cancer Center pilot project funds to JKR.

Cancer-associated fibroblasts-derived exosomes suppresses immune cell function in breast cancer via miR-92/PD-L1 pathway

2020 ◽  
Author(s):  
Dongwei Dou ◽  
Xiaoyang Ren ◽  
Mingli Han ◽  
Xiaodong Xu ◽  
Xin Ge ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Tumor Progression ◽  
Cancer Cells ◽  
Immune Suppression ◽  
Chromatin Immunoprecipitation ◽  
Breast Cancer Cells ◽  
Nuclear Translocation ◽  
Luciferase Assay ◽  
Cancer Associated Fibroblasts

Abstract Background Cancer associated fibroblasts (CAF) are important component in tumor microenvironment and has been reported contributes to tumor progression through many mechanisms, however, the detailed mechanism underling immune-suppression effect are not clearly defined. Methods In this study, human breast cancer-derived cancer associated fibroblasts was cultured, and CAF-derived exosomes in culture medium was isolated. Cancer cell migration was evaluated by transwell and wound healing assay, miR-92 binding to the LATS2 3’ untranslated region was validated by luciferase report assay, and underlying mechanism was investigated by chromatin immunoprecipitation and Immunoprecipitation. Results After treatment by CAF-derived exosomes, breast cancer cells express higher PD-L1, accompanied with increased miR-92 expression. Increased PD-L1 expression which induced by CAF- derived exosomes significantly promotes apoptosis and impaired proliferation of T cell. proliferation and migration of breast cancer cells was increased after transfection of miR-92, LATS2 was recognized as target gene of miR-92, which was proved by luciferase assay. Immunoprecipitation (IP) shown that LATS2 can interact with YAP1, after nuclear translocation, YAP1 could binds to enhancer region of PD-L1 to promotes transcription activity, which was confirmed by chromatin immunoprecipitation (ChIP). Furthermore, animal study confirmed that cancer associated fibroblasts significantly promotes tumor progression and impaired function of tumor infiltrated immune cells in vivo. Conclusion Our data revealed a novel mechanism which can induce immune suppression in tumor microenvironment.

scholarly journals Arctigenin Attenuates Breast Cancer Progression through Decreasing GM-CSF/TSLP/STAT3/β-Catenin Signaling

2020 ◽  
Vol 21 (17) ◽  
pp. 6357
Author(s):  
Hui Shi ◽  
Luping Zhao ◽  
Xinlin Guo ◽  
Runping Fang ◽  
Hui Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Nuclear Translocation ◽  
Breast Cancer Progression ◽  
Gm Csf ◽  
Stat3 Phosphorylation

Invasive breast cancer is highly regulated by tumor-derived cytokines in tumor microenvironment. The development of drugs that specifically target cytokines are promising in breast cancer treatment. In this study, we reported that arctigenin, a bioactive compound from Arctium lappa L., could decrease tumor-promoting cytokines GM-CSF, MMP-3, MMP-9 and TSLP in breast cancer cells. Arctigenin not only inhibited the proliferation, but also the invasion and stemness of breast cancer cells via decreasing GM-CSF and TSLP. Mechanistically, arctigenin decreased the promoter activities of GM-CSF and TSLP via reducing the nuclear translocation of NF-κB p65 which is crucial for the transcription of GM-CSF and TSLP. Furthermore, arctigenin-induced depletion of GM-CSF and TSLP inhibited STAT3 phosphorylation and β-catenin signaling resulting in decreased proliferation, invasion and stemness of breast cancer cells in vitro and in vivo. Our findings provide new insights into the mechanism by which tumor-promoting cytokines regulate breast cancer progression and suggest that arctigenin is a promising candidate for cytokine-targeted breast cancer therapy.

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