Role of c-Myc in Estrogen Stimulated Cell Proliferation in Normal and Malignant Breast Epithelial Cells

2001 ◽  
Author(s):  
Eileen Rogen
2020 ◽  
Author(s):  
Lin Cao ◽  
Xin Wang ◽  
Juhong Yang ◽  
Jia Guo ◽  
Xiang Li ◽  
...  

Abstract Background Neural cell adhesion molecule (NCAM), a common mammalian cell surface glycoprotein, is the major substrate of polysialic acid (PSA). Polysialylated NCAM occurs in many types of cancer, but rarely in normal adult tissues. Epithelial-mesenchymal transition (EMT) is an important process contributing to tumor metastasis. The functional role of NCAM hypersialylation in EMT is unclear. Method Expression of NCAM and PSA-NCAM in breast cancer progression were evaluated by western blot (WB), immunohistochemistry, semi-quantitative PCR and immunoprecipitation (IP). Overexpression of NCAM-140 and STX were performed to assess the functional role of NCAM hypersialylation by liposome transfection. Then, the cell proliferation ability was investigated with MTT assay. Transwell and wound closure assay were conducted to evaluate cell migratory ability. Phagokinetic gold sol assay and cell adhesion assay were performed to assess cell motility ability and cell adhesion ability, respectively. Furthermore, WB and IP were used to reveal the activated signaling pathway. Results The present study indicates that NCAM and attached polysialic acid affect behaviors of breast epithelial cells through differential signaling pathways, based on the following observations: (i) NCAM and PSA-NCAM were aberrantly regulated in breast cancer cells; (ii) NCAM and PSA-NCAM expression were upregulated in normal breast epithelial cells undergoing EMT; (iii) NCAM overexpression induced EMT in breast epithelial cells; (iv) NCAM promoted cell proliferation and migration through activation of a β-catenin/slug signaling pathway; (v) modification of PSA attached to NCAM inhibited cell adhesion and promoted cell motility through activation of an EGFR/STAT3 pathway. Conclusion These observations help clarify the molecular mechanisms whereby PSA and its major substrate NCAM modulate cell behaviors, and the significance of increased PSA expression on NCAM during EMT and tumor development.


2018 ◽  
Vol 73 (5) ◽  
pp. 289-293
Author(s):  
Evgeniya V. Shakhristova ◽  
Elena A. Stepovaya ◽  
Evgeniy V. Rudikov ◽  
Olga S. Sushitskaya ◽  
Daria O. Rodionova ◽  
...  

Background: Redox status imbalance against the backdrop of oxidative stress development underlies the pathogenesis of a whole range of diseases. Many intracellular proteins contain free thiol groups and undergo redox regulation which is one of the key processes in controlling cell proliferation. Thioredoxin and glutaredoxin are involved in maintaining intracellular redox homeostasis and act as candidates in regulating proliferation. This provides prospects for future development of methods for diagnosis and targeted therapy of socially sensitive diseases accompanied by oxidative stress. The aim of the study is to reveal the role of redox proteins in molecular mechanisms of regulating HBL-100 breast epithelial cell proliferation under the effect of roscovitine, a cell cycle inhibitor. Materials and methods: Two research groups were formed. They included HBL-100 human breast epithelial cells incubated in the presence and absence of 20 mcM roscovitine for 18 hours. The intracellular thioredoxin levels were determined using Western blot analysis with specific monoclonal antibodies. Distribution of the cells among cell cycle phases were evaluated by flow cytometry. The activity of glutathione reductase, glutathione peroxidase, and thioredoxin reductase were measured by spectrophotometry. Results: Under the effect of roscovitine in the HBL-100 cells, cell cycle arrest in the G2/М phases occurred and oxidative stress developed. In the meantime, the decrease in the thioredoxin and glutaredoxin concentrations was registered along with the change in the functional activity of glutathione-dependent enzymes. Conclusions: Application of roscovitine, a cell cycle inhibitor, allowed creating a model of oxidative stress in the breast epithelial cells against the backdrop of inhibited cell proliferation. We identified that thioredoxin and glutaredoxin contributed to impairment of cell cycle progression. It points at a possibility to regulate cell proliferation by modulating the functional features of cellular redox-dependent proteins in different pathologies accompanied by oxidative stress.


PLoS ONE ◽  
2012 ◽  
Vol 7 (7) ◽  
pp. e41355 ◽  
Author(s):  
Bin Wang ◽  
Linsey E. Lindley ◽  
Virneliz Fernandez-Vega ◽  
Megan E. Rieger ◽  
Andrew H. Sims ◽  
...  

2010 ◽  
Author(s):  
Guadalupe Lorenzatti ◽  
Anupama Pal ◽  
Wei Huang ◽  
Ana M. Cabanillas ◽  
Celina G. Kleer

2000 ◽  
Vol 68 (2) ◽  
pp. 124-132 ◽  
Author(s):  
Veena Bhalla ◽  
Kusum Joshi ◽  
Harpreet Vohra ◽  
Gurpreet Singh ◽  
Nirmal K. Ganguly

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