The Activation of Extracellular Signal-Regulated Kinase (ERK)/Mitogen-Activated Protein Kinase (MAPK) Signal Transduction Pathway on Invasive Growth of Breast Cancer

2020 ◽  
Vol 10 (7) ◽  
pp. 1005-1009
Author(s):  
Wei Ma ◽  
Lie Ma ◽  
Shaoqi Yang ◽  
Kai Wang

ERK/MAPK signal transduction pathway participates in occurrence and progression of breast cancer. This study utilized epidermal growth factor (EGF) and ERK antagonist PD98059 to analyze ERK/MAPK signal's role in breast cancer cells. Breast cancer MCF-7 cell line was separated into control group, EGF group, PD98059 group and EGF+ PD98059 group. Cell proliferation activity was assessed by MTT, whilst TUNEL was to describe cell apoptosis. Transwell assay was employed for cell invasion and migration. Protein expression of ERK1/2 and p-ERK1/2. Compared to control group, EGF treatment elevated cell proliferation or invasion/migration and decreased apoptosis at 6 h, 12 h and 24 h. PD98059 treatment decreased proliferation activity or cell invasion/migration, and enhanced apoptosis. Treatment of EGF plus PD98059 further decreased proliferation and invasion/migration compared to EGF group, but with higher level than PD98059 group (p < 0 05). EGF treatment elevated ERK1/2 and pERK1/2, PD98059 group had lower ERK1/2 or pERK1/2 expression, whilst EGF plus PD98059 treatment further decreased ERK1/2 and pERK1/2 expression (p < 0 05). EGF can regulate proliferation and invasion of breast cancer MCF-7 cells via ERK/MAPK signaling.

2020 ◽  
Vol 28 ◽  
Author(s):  
Fei Shao ◽  
Xiaonan Pang ◽  
Gyeong Hun Baeg

Abstract:: Breast cancer is the most common malignant tumor in women worldwide. Traditional ways of treatment, includ-ing radiotherapy and endocrine therapy, for breast cancer have inevitable side effects. In recent decades, targeted therapies for breast cancer have rapidly advanced and shown a promising future. The JAK/STAT signaling pathway has been shown to play important roles in tumorigenesis, maintenance and metastasis of breast cancer. Hence, many small molecule inhibi-tors of JAK and STAT proteins have been developed. These inhibitors exhibit potent inhibitory effects on breast cancer in both cellular and animal models, and even some of them have already been in clinical trials. This review article discussed the JAK/STAT signal transduction pathway in the pathogenesis of breast cancer, and the potential for the application of JAK/STAT inhibitors in breast cancer treatment.


2017 ◽  
Vol 4 (1) ◽  
pp. 47-58 ◽  
Author(s):  
Jens C. Hahne ◽  
Jorg B. Engel ◽  
Arnd Honig ◽  
Susanne R. Meyer ◽  
Domenico Zito ◽  
...  

2021 ◽  
Author(s):  
Yi-En Yao ◽  
Qi-Xiang Sun ◽  
Jing-Hong Zhang ◽  
Jian-Lin Huang ◽  
Si-Yue Xu ◽  
...  

Abstract Background: Mycobacterium vaccae nebulization imparted protective effect against asthma in a mouse model. The Jagged2-γδT17 signal transduction pathway plays an important role in bronchial asthma. However, the effect of M. vaccae nebulization on the Jagged2-γδT17 signal transduction pathway in mouse models of asthma remains unclear. Methods: In total, 30 female C57 mice were randomized to normal control (group a), asthma control (group b), M. vaccae nebulization prevention,and M. vaccae nebulization treatment (group d) groups. Asthma mice models were created using ovalbumin (OVA). The Notch signaling pathway was blocked by DAPT inhibitors. Airway hyperreactivity (AHR) was measured by noninvasive lung function tests. Histopathological analyses using blue-periodic acid Schiff along with hematoxylin and eosin were performed. Immunohistochemistry, immunofluorescence, and a Western blotting assay allowed for the detection of lung protein expressions, while spleen expressions of IL-17+γδT+ cytokines were assessed with FLOW cytometry. One-way analysis of variance for within-group comparisons, the least significant difference t-test or Student-Newman-Keuls test for intergroup comparisons, and the nonparametric rank sum test for analysis of airway inflammation scores were used in the study. Results: Asthmatic mice models demonstrated downregulated Notch signaling pathway activation and decreased γδT cells and IL-17 cytokine secretion. There was also increased Jagged2 protein expression which correlated positively with γδT+IL-17+ secretion. In asthmatic mice, the expressions of Jagged2 and γδT17, along with airway inflammation and airway reactivity, were all decreased after M. vaccae exposure (p<0.05). Conclusion: The Notch signaling pathway contributed towards asthma initiation and progression by facilitating γδT cells and IL-17 cytokines production. Inhaled M. vaccae led to a significant decrease in Jagged2 and γδT17 expressions in asthmatic mice, indicating its utility in asthma prevention.


2018 ◽  
Vol 96 (6) ◽  
pp. 825-831 ◽  
Author(s):  
Shuangzhen Bao ◽  
Xinying Wang ◽  
Zhichao Wang ◽  
Jinqiang Yang ◽  
Fangzhen Liu ◽  
...  

Despite the great progress in recent years, many aspects of the pathogenesis and progression of breast cancer remain unclear. A better understanding on the molecular mechanisms underlying metastasis and recurrence is crucial to improve the treatment of this lethal disease. MCF-7 cells were xenografted into mice until visible tumors developed, and the cells from tumor tissue and adjacent normal tissue were cultured with 3 passages as mass tumor (MT) cells and invasive tumor (IT) cells, respectively. Microarray analysis was performed to detect several viable microRNAs in these 2 types of cells. Further, miR-30 knockdown was used to investigate its role in tumor aggression. Relative levels of miR-30 were significantly higher in IT cells than MT cells. Knockdown of miR-30 in both MT and IT cells lowered cell proliferation and cell invasion abilities, and thus increased the survival time of mice xenografted with tumor cells. This study suggested that the knockdown of miR-30 decreased proliferation and invasion of carcinoma cells, giving rise to the potential of miR-30 as a tumor target or marker candidate for breast cancer therapy.


2005 ◽  
Vol 83 (1) ◽  
pp. 1-14 ◽  
Author(s):  
Katherine L Dunn ◽  
Paula S Espino ◽  
Bojan Drobic ◽  
Shihua He ◽  
James R Davie

Stimulation of the Ras-mitogen-activated protein kinase (MAPK) signal transduction pathway results in a multitude of events including expression of the immediate-early genes, c-fos and c-myc. Downstream targets of this stimulated pathway are the mitogen- and stress-activated protein kinases (MSK) 1 and 2, which are histone H3 kinases. In chromatin immunoprecipitation assays, it has been shown that the mitogen-induced phosphorylated H3 is associated with the immediate-early genes and that MSK1/2 activity and H3 phosphorylation have roles in chromatin remodeling and transcription of these genes. In oncogene-transformed fibroblasts in which the Ras-MAPK pathway is constitutively active, histone H1 and H3 phosphorylation is increased and the chromatin of these cells has a more relaxed structure than the parental cells. In this review we explore the deregulation of the Ras-MAPK pathway in cancer, with an emphasis on breast cancer. We discuss the features of MSK1 and 2 and the impact of a constitutively activated Ras-MAPK pathway on chromatin remodeling and gene expression.Key words: Ras, mitogen-activated protein kinase signal transduction pathway, histone H3 phosphorylation, MSK1, breast cancer.


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