Evidence that TRPM7 is required for breast cancer cell proliferation

2009 ◽  
Vol 297 (3) ◽  
pp. C493-C502 ◽  
Author(s):  
Arnaud Guilbert ◽  
Mathieu Gautier ◽  
Isabelle Dhennin-Duthille ◽  
Nathalie Haren ◽  
Henri Sevestre ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Dependent Manner ◽  
Cancer Cell Proliferation ◽  
Human Breast ◽  
Breast Cancer Cell Proliferation ◽  
Inward Current ◽  
Mcf 7

Because transient receptor potential (TRP) channels have been implicated in tumor progression, we have investigated the potential role of TRPM7 channel in breast cancer cell proliferation. Under whole cell patch clamp, a Mg2+-inhibited cationic (MIC) current was observed in MCF-7 cells. This current was characterized by an inward current and a strong outward rectifying current that were both inhibited in a concentration-dependent manner by the presence of intracellular Mg2+ or Mg2+-ATP. The inward current was reduced by La3+, and the outward current was sensitive to 2-aminoethoxydiphenyl borate (2-APB), spermine, La3+, and flufenamic acid. Importantly, a similar MIC current was also recorded in the primary culture of human breast cancerous epithelial cells (hBCE). Moreover, TRPM7 transcripts were found in both hBCE and MCF-7 cells. In MCF-7 cells, the MIC current was inhibited by TRPM7 small interfering RNA. Interestingly, we found that cell proliferation and intracellular Ca2+ concentration were also reduced by TRPM7 silencing in MCF-7 cells. TRPM7 channels were also found in both human breast cancer and healthy tissues. Importantly, TRPM7 channel was overexpressed in grade III breast cancer samples associated with important Ki67 or tumor size. Our findings strongly suggest that TRPM7 is involved in the proliferative potentiality of breast cancer cells, probably by regulating Ca2+ influx.

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

Endocrinology ◽  
2017 ◽  
Vol 158 (12) ◽  
pp. 4218-4232 ◽  
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.

scholarly journals Estrogen-Like Properties of Fluorotelomer Alcohols as Revealed by MCF-7 Breast Cancer Cell Proliferation

2006 ◽  
Vol 114 (1) ◽  
pp. 100-105 ◽  
Author(s):  
Marleen Maras ◽  
Caroline Vanparys ◽  
Frederik Muylle ◽  
Johan Robbens ◽  
Urs Berger ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Cell Proliferation ◽  
Fluorotelomer Alcohols ◽  
Mcf 7

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

2012 ◽  
Vol 6 ◽  
pp. BCBCR.S9592 ◽  
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.

scholarly journals p53–GSDME Elevation: A Path for CDK7 Inhibition to Suppress Breast Cancer Cell Survival

2021 ◽  
Vol 8 ◽  
Author(s):  
Yueyuan Wang ◽  
Jingyu Peng ◽  
Xuguang Mi ◽  
Ming Yang
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cell Survival ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Colony Formation ◽  
Dependent Manner ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Cell Proliferation ◽  
Cancer Cell Survival

Higher cyclin-dependent kinase (CDK7) expression is a character of breast cancer and indicates poor prognosis. Inhibiting CDK7 exhibited effective cancer cell suppression which implies the potential of CDK7 inhibition to be a method for anti-cancer treatment. Our study aimed to explore a novel mechanism of CDK7 inhibition for suppressing breast cancer cell survival. Here, we proved inhibiting CDK7 repressed breast cancer cell proliferation and colony formation and increased the apoptotic cell rate, with p53 and GSDME protein level elevation. When p53 was suppressed in MCF-7 cells, the decline of GSDME expression and associated stronger proliferation and colony formation could be observed. Since downregulation of GSDME was of benefit to breast cancer cells, p53 inhibition blocked the elevation of GSDME induced by CDK7 inhibition and retrieved cells from the tumor suppressive effect of CDK7 inhibition. Therefore, CDK7 inhibition exerted a negative effect on breast cancer cell proliferation and colony formation in a p53–GSDME dependent manner. These results revealed the CDK7–p53–GSDME axis could be a pathway affecting breast cancer cell survival.

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