Inhibition of MCF-7 breast cancer cell proliferation and in vivo steroid sulphatase activity by 2-methoxyoestradiol-bis-sulphamate

AbstractProtein arginine methyltransferase 1 (PRMT1) is able to promote breast cancer cell proliferation. However, the detailed mechanisms of PRMT1-mediated breast cancer cell proliferation are largely unknown. In this study, we reveal that PRMT1-mediated methylation of EZH2 at the R342 site (meR342-EZH2) has a great effect on PRMT1-induced cell proliferation. We also demonstrate that meR342-EZH2 can accelerate breast cancer cell proliferation in vitro and in vivo. Further, we show that meR342-EZH2 promotes cell cycle progression by repressing P16 and P21 transcription expression. In terms of mechanism, we illustrate that meR342-EZH2 facilitates EZH2 binding with SUZ12 and PRC2 assembly by preventing AMPKα1-mediated phosphorylation of pT311-EZH2, which results in suppression of P16 and P21 transcription by enhancing EZH2 expression and H3K27me3 enrichment at P16 and P21 promoters. Finally, we validate that the expression of PRMT1 and meR342-EZH2 is negatively correlated with pT311-EZH2 expression. Our findings suggest that meR342-EZH2 may become a novel therapeutic target for the treatment of breast cancer.

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Exendin-4, a Glucagonlike Peptide-1 Receptor Agonist, Attenuates Breast Cancer Growth by Inhibiting NF-κB Activation

Endocrinology ◽

10.1210/en.2017-00461 ◽

2017 ◽

Vol 158 (12) ◽

pp. 4218-4232 ◽

Cited By ~ 18

Author(s):

Chikayo Iwaya ◽

Takashi Nomiyama ◽

Shiho Komatsu ◽

Takako Kawanami ◽

Yoko Tsutsumi ◽

...

Keyword(s):

Breast Cancer ◽

Diabetes Mellitus ◽

Cell Proliferation ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Cancer Tissue ◽

Dependent Manner ◽

Cancer Cell Proliferation ◽

Breast Cancer Cell Proliferation ◽

Mcf 7

Abstract Incretin therapies have received much attention because of their tissue-protective effects, which extend beyond those associated with glycemic control. Cancer is a primary cause of death in patients who have diabetes mellitus. We previously reported antiprostate cancer effects of the glucagonlike peptide-1 (GLP-1) receptor (GLP-1R) agonist exendin-4 (Ex-4). Breast cancer is one of the most common cancers in female patients who have type 2 diabetes mellitus and obesity. Thus, we examined whether GLP-1 action could attenuate breast cancer. GLP-1R was expressed in human breast cancer tissue and MCF-7, MDA-MB-231, and KPL-1 cell lines. We found that 0.1 to 10 nM Ex-4 significantly decreased the number of breast cancer cells in a dose-dependent manner. Although Ex-4 did not induce apoptosis, it attenuated breast cancer cell proliferation significantly and dose-dependently. However, the dipeptidyl peptidase-4 inhibitor linagliptin did not affect breast cancer cell proliferation. When MCF-7 cells were transplanted into athymic mice, Ex-4 decreased MCF-7 tumor size in vivo. Ki67 immunohistochemistry revealed that breast cancer cell proliferation was significantly reduced in tumors extracted from Ex-4-treated mice. In MCF-7 cells, Ex-4 significantly inhibited nuclear factor κB (NF-κB ) nuclear translocation and target gene expression. Furthermore, Ex-4 decreased both Akt and IκB phosphorylation. These results suggest that GLP-1 could attenuate breast cancer cell proliferation via activation of GLP-1R and subsequent inhibition of NF-κB activation.

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Radiation-Triggered NF-κB Activation is Responsible for the Angiogenic Signaling Pathway and Neovascularization for Breast Cancer Cell Proliferation and Growth

Breast Cancer Basic and Clinical Research ◽

10.4137/bcbcr.s9592 ◽

2012 ◽

Vol 6 ◽

pp. BCBCR.S9592 ◽

Cited By ~ 2

Author(s):

Hui Yu ◽

Sumathy Mohan ◽

Mohan Natarajan

Keyword(s):

Breast Cancer ◽

Cell Proliferation ◽

Endothelial Cells ◽

Radiation Exposure ◽

Signaling Pathway ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Cancer Cell Proliferation ◽

Breast Cancer Cell Proliferation ◽

Mcf 7

Tumors require blood supply to survive, grow, and metastasize. This involves the process of angiogenesis signaling for new blood vessel growth into a growing tumor mass. Understanding the mechanism of the angiogenic signaling pathway and neovascularization for breast cancer cell proliferation and growth would help to develop molecular interventions and achieve disease free survival. Our hypothesis is that the surviving cancer cell(s) after radiotherapy can initiate angiogenic signaling pathway in the neighboring endothelial cells resulting in neovascularization for breast cancer cell growth. The angiogenic signaling pathway is initiated by angiogenic factors, VEGF and FGF-2, through activation of a transcriptional regulator NF-κB, which in turn is triggered by therapeutic doses of radiation exposure Human breast adenocarcinoma cells (MCF-7 cells) were exposed to Cesium-137 (137Cs) γ rays to a total dose of 2 Gy at a dose rate of 1.03 Gy/min. The results of mobility shift assay showed that radiation at clinical doses (2 Gy) could induce NF-κB DNA-binding activity. Then, we examined the communication of angiogenic signals from irradiated MCF-7 cells to vascular endothelial cells. At the protein level, the western blot showed induction of angiogenic factors VEGF and FGF-2 in MCF-7 cells irradiated with 2 Gy. Inhibition of NF-κB activation attenuated VEGF and FGF-2 levels. These factors are secreted into the medium. The levels of VEGF and FGF-2 in the extra cellular medium were both increased, after 2 Gy exposures. We also observed corresponding expression of VEGFR2 and FGFR1 in non-irradiated endothelial cells that were co-cultured with irradiated MCF-7 cells. In support of this, in vitro tube formation assays provided evidence that irradiated MCF-7 cells transmit signals to potentiate cultured non-irradiated endothelial cells to form tube networks, which is the hallmark of neovascularization. Inhibition of NF-κB activation attenuated irradiated MCF-7-induced tube network formation. The data provide evidence that the radiation exposure is responsible for tumor growth and maintenance by inducing an angiogenic signaling pathway through activation of NF-κB.

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MiR-765 Regulates Breast Cancer Cell Proliferation, Apoptosis, and Adriamycin Resistance Through Targeting Epithelial Membrane Protein 3

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2020.2400 ◽

2020 ◽

Vol 10 (8) ◽

pp. 1193-1198

Author(s):

Siyi Li ◽

Hongjuan Peng ◽

Jianwen Li

Keyword(s):

Breast Cancer ◽

Cell Proliferation ◽

Membrane Protein ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Resistant Cell ◽

Resistant Cell Line ◽

Cancer Cell Proliferation ◽

Breast Cancer Cell Proliferation ◽

Mcf 7

Epithelial membrane protein 3 (EMP3) regulates cell proliferation, differentiation, and apoptosis. Bioinformatics analysis revealed that miR-765 had complimentary sequence with the 3 -URT of EMP3 mRNA. miR-765 regulates EMP3 and influences breast cancer cell behaviors. However, it is unclear whether this regulation plays a role in affecting drug resistance. Our study assessed miR765's role in EMP3 expression and adriamycin (ADM) resistance of breast cancer. ADM resistant cell line MCF-7/ADM was established and assigned into miR-NC group, miR-765 mimic group, siRNA-NC group, and siRNA-EMP3 group followed by analysis of cell proliferation and apoptosis. miR-765 targets EMP3. The miR-765 level and apoptosis rate in MCF-7/ADM cells were significantly lower, while EMP3 level and cell proliferation were higher than MCF-7 cells. miR-765 mimic or siRNA-EMP3 significantly downregulated EMP3, weakened cell proliferation, increased apoptosis, and decreased ADM resistance. MiR-765 and EMP3 involves in ADM resistance of breast cancer cells. Up-regulation of miR-765 inhibits breast cancer cell proliferation and reduces ADM resistance via regulating EMP3.

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ChemInform Abstract: Substituted-Vinyl Hydroxytriarylethylenes, 1-(4-(2-(Diethylamino)ethoxy)phenyl)-1-(4-hydroxyphenyl)-2-phenylethylenes: Synthesis and Effects on MCF 7 Breast Cancer Cell Proliferation.

ChemInform ◽

10.1002/chin.198718134 ◽

1987 ◽

Vol 18 (18) ◽

Author(s):

P. C. RUENITZ ◽

J. R. BAGLEY ◽

C. K. W. WATTS ◽

R. E. HALL ◽

R. L. SUTHERLAND

Keyword(s):

Breast Cancer ◽

Cell Proliferation ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Cancer Cell Proliferation ◽

Breast Cancer Cell Proliferation ◽

Mcf 7

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The effect of AH 26 and AH Plus on MCF-7 breast cancer cell proliferation in vitro

International Endodontic Journal ◽

10.1046/j.1365-2591.2002.00531.x ◽

2002 ◽

Vol 35 (6) ◽

pp. 551-556 ◽

Cited By ~ 5

Author(s):

R. Pulgar ◽

J. J. Segura-Egea ◽

M. F. Fernandez ◽

A. Serna ◽

N. Olea

Keyword(s):

Breast Cancer ◽

Cell Proliferation ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Cancer Cell Proliferation ◽

Breast Cancer Cell Proliferation ◽

Ah Plus ◽

Proliferation In Vitro ◽

Mcf 7

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Oncogenic action of the exosome cofactor RBM7 by stabilization of CDK1 mRNA in breast cancer

npj Breast Cancer ◽

10.1038/s41523-020-00200-w ◽

2020 ◽

Vol 6 (1) ◽

Author(s):

Pei-Wen Xi ◽

Xu Zhang ◽

Lei Zhu ◽

Xin-Yuan Dai ◽

Lin Cheng ◽

...

Keyword(s):

Breast Cancer ◽

Cell Proliferation ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Rna Binding ◽

Cancer Cell Proliferation ◽

Breast Cancer Cell Proliferation ◽

Rna Exosome

Abstract RNA exosome can target the specific RNAs for their processing/degradation by distinct exosome cofactors. As a key component in exosome cofactors, RNA binding motif protein 7 (RBM7) shows the binding specificity for uridine-rich sequences in mRNAs via its RNA recognition motifs. However, the specific function of RBM7 in human breast cancer remains unclear. In vitro, experiments revealed that knockdown of RBM7 dramatically inhibited breast cancer cell proliferation, while inducing G1 cell cycle arrest; the opposite was true when RBM7 was overexpressed. Meanwhile, experiments in vivo confirmed the oncogenic function of RBM7 in breast cancer. RNA sequencing and the following pathway analysis found that cyclin-dependent kinase1 (CDK1) was one of the main gene regulated by RBM7. Overexpression of RBM7 increased CDK1 expression, while RBM7 knockdown decreased it. RIP assays additionally found that RBM7 bound directly to CDK1 mRNA. It was also showed that RBM7 could directly bind to the AU-rich elements (AREs) in 3′-UTR of CDK1 mRNA, which contributed to the stability of CDK1 mRNA by lengthening its half-life. More importantly, the oncogenic activity reduced by knockdown of RBM7 could be rescued by overexpression of CDK1 both in vitro and in vivo, but mutant CDK1 failed. All the evidences implied RBM7 promoted breast cancer cell proliferation by stabilizing CDK1 mRNA via binding to AREs in its 3′-UTR. As we knew, it was the first attempt to connect the RNA exosome to the tumor development, providing new insights into the mechanisms of RNA exosome-linked diseases.

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