scholarly journals Baicalin inhibits breast cancer development via inhibiting IĸB kinase activation in vitro and in vivo

2018 ◽  
Author(s):  
Yang Gao ◽  
Hui Liu ◽  
Hongzhi Wang ◽  
Hailong Hu ◽  
Hongjuan He ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Development ◽  
Kinase Activation ◽  
Breast Cancer Development

scholarly journals The Effects of Adipocytes on the Regulation of Breast Cancer in the Tumor Microenvironment: An Update

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 857 ◽  
Author(s):  
Chu ◽  
Phuong ◽  
Tien ◽  
Tran ◽  
Nguyen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Tumor Therapy ◽  
Cancer Development ◽  
Systemic Review ◽  
Breast Cancer Development ◽  
Invasion And Migration ◽  
Metabolic Substrates

Obesity is a global pandemic and it is well evident that obesity is associated with the development of many disorders including many cancer types. Breast cancer is one of that associated with a high mortality rate. Adipocytes, a major cellular component in adipose tissue, are dysfunctional during obesity and also known to promote breast cancer development both in vitro and in vivo. Dysfunctional adipocytes can release metabolic substrates, adipokines, and cytokines, which promote proliferation, progression, invasion, and migration of breast cancer cells. The secretion of adipocytes can alter gene expression profile, induce inflammation and hypoxia, as well as inhibit apoptosis. It is known that excessive free fatty acids, cholesterol, triglycerides, hormones, leptin, interleukins, and chemokines upregulate breast cancer development. Interestingly, adiponectin is the only adipokine that has anti-tumor properties. Moreover, adipocytes are also related to chemotherapeutic resistance, resulting in the poorer outcome of treatment and advanced stages in breast cancer. Evaluation of the adipocyte secretion levels in the circulation can be useful for prognosis and evaluation of the effectiveness of cancer therapy in the patients. Therefore, understanding about functions of adipocytes as well as obesity in breast cancer may reveal novel targets that support the development of new anti-tumor therapy. In this systemic review, we summarize and update the effects of secreted factors by adipocytes on the regulation of breast cancer in the tumor microenvironment.

scholarly journals ERK knockdown suppress cell biological activities via regulation CD59 in breast cancer

2021 ◽  
Author(s):  
Fei Qu ◽  
Yanru Cui ◽  
Shixin Yang ◽  
Zhihua Li ◽  
Jingxian Ding ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Biological Activities ◽  
Cell Number ◽  
Tunel Assay ◽  
Cancer Development ◽  
Breast Cancer Cell Lines ◽  
Breast Cancer Development

IntroductionIt has been unclear that ERK play the effects and relative mechanism in breast cancer development. The purpose of this work was to discuss the ERK play the effect in breast cancer and relative mechanisms.Material and methodsEvaluating ERK and CD59 proteins expression in difference tissue from patients by IHC assay. Using MCF-7 and MDA-MB-231 cell lines which were breast cancer cell lines as target cell lines in our study. In vitro study, evaluating cell biological activities including proliferation, apoptosis, cell cycle, invasion, adherent and migration by MTT, clone test, TUNEL assay, flow cytometry and wound healing. And measuring relative proteins expressions by WB assay. In vivo study, measuring tumor weight and volume, the apoptosis cell number were evaluated by TUNEL assay and relative proteins expressions by IHC assay.ResultsCompared with adjacent normal tissue, the ERK and CD59 proteins expression were significantly increased in breast cancer tissues (P＜0.001, respectively).In vitro and vivo studies, with ERK knockdown, the cell biological activities were significantly depressed with CD59 suppressing (P＜0.001, respectively). And the relative proteins including CD59, PKD, P53, E-cadherin and Vimentin were significantly differences (P＜0.001, respectively).ConclusionsERK play an oncology gene in breast cancer development, ERK inhibitor had effects to suppress breast cancer biological via regulation CD59 in vitro and vivo study.

scholarly journals MRCKα Is Dispensable for Breast Cancer Development in the MMTV-PyMT Model

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 942
Author(s):  
Mei Qi Kwa ◽  
Rafael Brandao ◽  
Trong H. Phung ◽  
Jianfeng Ge ◽  
Giuseppe Scieri ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression Signature ◽  
Genomic Analysis ◽  
Cancer Development ◽  
Breast Cancer Cell Lines ◽  
Normal Mammary Gland ◽  
Breast Cancers ◽  
Human Breast ◽  
Breast Cancer Development

MRCKα is a ubiquitously expressed serine/threonine kinase involved in cell contraction and F-actin turnover, which is highly amplified in human breast cancer and part of a gene expression signature for bad prognosis. Nothing is known about the in vivo function of MRCKα. To explore MRCKα function in development and in breast cancer, we generated mice lacking a functional MRCKα gene. Mice were born close to the Mendelian ratio and showed no obvious phenotype including a normal mammary gland formation. Assessing breast cancer development using the transgenic MMTV-PyMT mouse model, loss of MRCKα did not affect tumor onset, tumor growth and metastasis formation. Deleting MRCKα and its related family member MRCKβ in two triple-negative breast cancer cell lines resulted in reduced invasion of MDA-MB-231 cells, but did not affect migration of 4T1 cells. Further genomic analysis of human breast cancers revealed that MRCKα is frequently co-amplified with the oncogenes ARID4B and AKT3 which might contribute to the prognostic value of MRCKα expression. Collectively, these data suggest that MRCKα might be a prognostic marker for breast cancer, but probably of limited functional importance.

scholarly journals Luteolin Inhibits Breast Cancer Development and Progression In Vitro and In Vivo by Suppressing Notch Signaling and Regulating MiRNAs

2015 ◽  
Vol 37 (5) ◽  
pp. 1693-1711 ◽  
Author(s):  
Da-Wei Sun ◽  
He-Da Zhang ◽  
Ling Mao ◽  
Chang-Fei Mao ◽  
Wei Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Notch Signaling ◽  
Notch Pathway ◽  
Tube Formation ◽  
Cancer Development ◽  
Notch 1 ◽  
Related Proteins

Background/Aims: This study aims to investigate the effect of Luteolin on breast cancer in vitro and in vivo and the interaction between miRNAs and Notch signaling after Luteolin intervention, and illustrates the possible underlying mechanism and regulation loop. Methods: Cell growth/survival assays and cell cycle analyses were performed to evaluate cell survival in vitro. Scratch tests, cell invasion assays and tube formation assays were carried out to analyze cell viability and identify the impact of Luteolin on angiogenesis. Critical components in the Notch pathway including proteins and mRNAs were detected by Western blotting analyses, ELISA assays and real-time reverse transcription-polymerase chain reaction. Matrix metalloproteinases activity was evaluated by gelatin zymography analyses. MiRNAs were analyzed by miRNA expression assays. After MDA-MB-231 cells were separately transfected with Notch-1 siRNA/cDNA and miRNA mimics, the above assays were also carried out to examine potential tumor cell changes. Xenograft models were applied to evaluate the treatment potency of Luteolin in breast cancer. Results: Luteolin significantly inhibited breast cancer cell survival, cell cycle, tube formation and the expression of Notch signaling-related proteins and mRNAs, and regulated miRNAs. After introducing Notch-1 siRNA and miRNA mimics, MDA-MB-231 cells presented with changes in miRNA levels, reduced Notch signaling-related proteins, and decreased tumor survival, invasion and angiogenesis. Conclusion: Luteolin inhibits Notch signaling by regulating miRNAs. However, the effect of miRNAs on the Notch pathway could be either Luteolin-dependent or Luteolin-independent. Furthermore, Notch-1 alteration may inversely change miRNAs levels. Our data demonstrates that Luteolin, miRNAs and the Notch pathway are critical in breast cancer development and prognosis.

scholarly journals Adaptive response to BET inhibition induces therapeutic vulnerability to MCL1 inhibitors in breast cancer

2019 ◽  
Author(s):  
Gonghong Yan ◽  
Heping Wang ◽  
Augustin Luna ◽  
Behnaz Bozorgui ◽  
Xubin Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lipid Metabolism ◽  
Adaptive Response ◽  
Structural Changes ◽  
Breast Cancers ◽  
Kinase Activation ◽  
Metabolism Enzymes ◽  
Chromosomal Amplifications

AbstractThe development of effective targeted therapies for the treatment of basal-like breast cancers remains challenging. Here, we demonstrate that BET inhibition induces a multi-faceted adaptive response program leading to MCL1 protein-driven evasion of apoptosis in breast cancers. Consequently, co-targeting MCL1 and BET is highly synergistic in in vitro and in vivo breast cancer models. Drug response and genomics analyses revealed that MCL1 copy number alterations, including low-level gains, are selectively enriched in basal-like breast cancers and associated with effective BET and MCL1 co-targeting. The mechanism of adaptive response to BET inhibition involves upregulation of critical lipid metabolism enzymes including the rate-limiting enzyme stearoyl-CoA desaturase (SCD). Changes in the lipid metabolism are associated with increases in cell motility and membrane fluidity as well as transitions in cell morphology and adhesion. The structural changes in the cell membrane leads to re-localization and activation of HER2/EGFR which can be interdicted by inhibiting SCD activity. Active HER2/EGFR, in turn, induces accumulation of MCL1 protein and therapeutic vulnerability to MCL1 inhibitors. The BET protein, lipid metabolism and receptor tyrosine kinase activation cascade is observed in patient cohorts of basal-like and HER2-amplified breast cancers. The high frequency of MCL1 chromosomal amplifications (>30%) and gains (>50%) in basal-like breast cancers suggests that BET and MCL1 co-inhibition may have therapeutic utility in this aggressive subtype.

scholarly journals tRNA queuosine modification enzyme modulates the growth and microbiome recruitment to breast tumors

2020 ◽  
Author(s):  
Jilei Zhang ◽  
Rong Lu ◽  
Yong-Guo Zhang ◽  
Żaneta Matuszek ◽  
Yinglin Xia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Mouse Model ◽  
Human Breast Cancer ◽  
Cancer Development ◽  
Human Breast ◽  
Mcf7 Cells ◽  
And Migration

Abstract Background: Transfer RNA (tRNA) queuosine (Q)-modifications occur specifically in 4 cellular tRNAs at the wobble anticodon position. tRNA Q-modification in human cells depends on the gut microbiome because the microbiome product queuine is required for its installation by the enzyme queuine tRNA ribosyltransferase catalytic subunit 1 (QTRT1) encoded in the human genome. Although tRNA Q-modification has been studied a long time regarding its properties in decoding and tRNA fragment generation, how QTRT1 affects tumorigenesis is still poorly understood. Results: We generated single clones of QTRT1-knockout breast cancer MCF7 cells using Double Nickase Plasmid. The impacts of QTRT1-delection on cell proliferation and migration in vitro were evaluated using cell culture, while the regulations on tumor growth in vivo were evaluated using xenograft BALB/c nude mouse model. We found that QTRT1 completely deleted from human breast cancer MCF7 cells could change the functions of regulation genes which are critical in cell proliferation, tight junction formation, and migration in human breast cancer cells in vitro and a breast tumor mouse model in vivo . We also found that microbiome maybe involved in the breast cancer development in vivo. Conclusions: Our results demonstrate that the QTRT1 gene and microbiome play a critical role in breast cancer development.

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