scholarly journals Protein expression of the Ets transcription factor Elf-1 in breast cancer cells is negatively correlated with histological grading, but not with clinical outcome

2011 ◽  
Author(s):  
J�rgen Dittmer
Keyword(s):  
Breast Cancer ◽  
Transcription Factor ◽  
Clinical Outcome ◽  
Protein Expression ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Histological Grading ◽  
Ets Transcription Factor

scholarly journals The Antiproliferative Effects of Progestins in T47D Breast Cancer Cells Are Tempered by Progestin Induction of the ETS Transcription Factor Elf5

2010 ◽  
Vol 24 (7) ◽  
pp. 1380-1392 ◽  
Author(s):  
H. N. Hilton ◽  
M. Kalyuga ◽  
M. J. Cowley ◽  
M. C. Alles ◽  
H. J. Lee ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Transcription Factor ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Gene Set Enrichment Analysis ◽  
Cell Phenotype ◽  
Cell Cycle Gene ◽  
Antiproliferative Effects ◽  
Ets Transcription Factor

Abstract Prolactin and progesterone act together to regulate mammary alveolar development, and both hormones have been implicated in breast cancer initiation and progression. Here we show that Elf5, a prolactin-induced ETS transcription factor that specifies the mammary secretory cell lineage, is also induced by progestins in breast cancer cells via a direct mechanism. To define the transcriptional response to progestin elicited via Elf5, we made an inducible Elf5 short hairpin-RNA knock-down model in T47D breast cancer cells and used it to prevent the progestin-induction of Elf5. Functional analysis of Affymetrix gene expression data using Gene Ontologies and Gene Set Enrichment Analysis showed enhancement of the progestin effects on cell cycle gene expression. Cell proliferation assays showed a more efficacious progestin-induced growth arrest when Elf5 was kept at baseline levels. These results showed that progestin induction of Elf5 expression tempered the antiproliferative effects of progestins in T47D cells, providing a further mechanistic link between prolactin and progestin in the regulation of mammary cell phenotype.

scholarly journals Integrin α3β1 Promotes Invasive and Metastatic Properties of Breast Cancer Cells through Induction of the Brn-2 Transcription Factor

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 480
Author(s):  
Rakshitha Pandulal Miskin ◽  
Janine S. A. Warren ◽  
Abibatou Ndoye ◽  
Lei Wu ◽  
John M. Lamar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Transcription Factor ◽  
Cancer Cells ◽  
Cell Invasion ◽  
Breast Cancer Cells ◽  
Gene Promoter ◽  
Akt Inhibitor ◽  
Integrin Α3β1

In the current study, we demonstrate that integrin α3β1 promotes invasive and metastatic traits of triple-negative breast cancer (TNBC) cells through induction of the transcription factor, Brain-2 (Brn-2). We show that RNAi-mediated suppression of α3β1 in MDA-MB-231 cells caused reduced expression of Brn-2 mRNA and protein and reduced activity of the BRN2 gene promoter. In addition, RNAi-targeting of Brn-2 in MDA-MB-231 cells decreased invasion in vitro and lung colonization in vivo, and exogenous Brn-2 expression partially restored invasion to cells in which α3β1 was suppressed. α3β1 promoted phosphorylation of Akt in MDA-MB-231 cells, and treatment of these cells with a pharmacological Akt inhibitor (MK-2206) reduced both Brn-2 expression and cell invasion, indicating that α3β1-Akt signaling contributes to Brn-2 induction. Analysis of RNAseq data from patients with invasive breast carcinoma revealed that high BRN2 expression correlates with poor survival. Moreover, high BRN2 expression positively correlates with high ITGA3 expression in basal-like breast cancer, which is consistent with our experimental findings that α3β1 induces Brn-2 in TNBC cells. Together, our study demonstrates a pro-invasive/pro-metastatic role for Brn-2 in breast cancer cells and identifies a role for integrin α3β1 in regulating Brn-2 expression, thereby revealing a novel mechanism of integrin-dependent breast cancer cell invasion.

scholarly journals Fluid flow exposure promotes Epithelial-to-Mesenchymal Transition and adhesion of breast cancer cells to endothelial cells

2020 ◽  
Author(s):  
Kenneth F. Fuh ◽  
Robert D. Shepherd ◽  
Jessica S. Withell ◽  
Brayden K. Kooistra ◽  
Kristina D Rinker
Keyword(s):  
Breast Cancer ◽  
Endothelial Cells ◽  
Fluid Flow ◽  
Network Analysis ◽  
Protein Expression ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Endothelial Monolayer ◽  
Mesenchymal Transition

Abstract Background: Fluid forces are an integral part of the tumor microenvironment through all phases of development and progression. However, it is not well understood how these forces affect key steps in the progression of breast cancer of Epithelial-to-Mesenchymal Transition (EMT) and adhesion to vascular wall endothelial cells. EMT is associated with the progression of most carcinomas through induction of new transcriptional programs within affected epithelial cells, resulting in cells becoming more motile and adhesive to endothelial cells.Methods: MDA-MB-231, SK-BR-3, BT-474, and MCF-7 cells and normal Human Mammary Epithelial Cells (HMECs) were exposed to fluid flow in a parallel-plate bioreactor system. Changes in gene expression were quantified using microarrays and qPCR, gene-gene interactions were elucidated using network analysis, and key modified genes were examined in clinical datasets. Changes in protein expression of key EMT markers between chemically induced EMT and flow-exposed cells were compared in immunocytochemistry assays. Finally, the ability of flow-stimulated and unstimulated cancer cells to adhere to an endothelial monolayer was evaluated in flow and static adhesion experiments.Results: Fluid flow stimulation resulted in upregulation of EMT inducers and downregulation of repressors. Specifically, Vimentin and Snail were upregulated both at the gene and protein expression levels in flow stimulated HMECs, suggesting progression towards an EMT phenotype. Flow-induced overexpression of a panel of cell adhesion genes was also observed. Network analysis revealed genes involved in cell flow responses including FN1, PLAU, and ALCAM. When evaluated in clinical datasets, overexpression of FN1, PLAU, and ALCAM was observed in patients with most subtypes of breast cancer. We also observed increased adhesion of flow-stimulated breast cancer cells compared to unstimulated controls, suggesting an increased potential to form secondary tumors at metastatic sites. Conclusions: This study shows that prolonged fluid force exposure on the order of 1 Pa promotes EMT and adhesion of breast cancer cells to an endothelial monolayer. Further, identified biomarkers were distinctly expressed in patient populations. A better understanding of how biophysical forces such as shear stress affect cellular processes involved in metastatic progression of breast cancer is important for identifying new molecular markers for disease progression, and for predicting metastatic risk.

scholarly journals Control of MYC-dependent apoptotic threshold by a co-amplified ubiquitin E3 ligase UBR5

2019 ◽  
Author(s):  
Xi Qiao ◽  
Ying Liu ◽  
Maria Llamazares Prada ◽  
Abhishekh Gupta ◽  
Alok Jaiswal ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protein Expression ◽  
Cancer Cells ◽  
Ubiquitin Ligase ◽  
Breast Cancer Cells ◽  
Human Cancer ◽  
Cancer Therapeutics ◽  
Cancer Tissue ◽  
Basal Type

AbstractMYC protein expression has to be tightly controlled to allow for maximal cell proliferation without inducing apoptosis. Here we discover UBR5 as a novel MYC ubiquitin ligase and demonstrate how it functions as a molecular rheostat to prevent excess accumulation of MYC protein. UBR5 effects on MYC protein stability are independent on N-terminal FBW7 degron of MYC. Endogenous UBR5 inhibition induces MYC protein expression and activates MYC target genes. Moreover, UBR5 governs MYC-dependent phenotypes in vivo in Drosophila. In cancer cells, UBR5-mediated MYC protein suppression diminishes cell killing activity of cancer therapeutics. Further, we demonstrate that UBR5 dominates MYC protein expression at the single-cell level in human basal-type breast cancer tissue. Myc and Ubr5 are co-amplified in MYC-driven human cancer types, and UBR5 controls MYC-mediated apoptotic threshold in co-amplified basal type breast cancer cells. In summary, UBR5 is a novel MYC ubiquitin ligase and an endogenous rheostat for MYC protein expression in vivo. Clinically, expression of UBR5 may be important for protection of breast cancer cells from drug-induced, and MYC-dependent, apoptosis.

scholarly journals Asiatic Acid Interferes with Invasion and Proliferation of Breast Cancer Cells by Inhibiting WAVE3 Activation through PI3K/AKT Signaling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Xiao-jun Gou ◽  
Huan-huan Bai ◽  
Li-wei Liu ◽  
Hong-yu Chen ◽  
Qi Shi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protein Expression ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Nude Mice ◽  
Breast Cancer Cells ◽  
Akt Signaling ◽  
Asiatic Acid ◽  
Akt Signaling Pathway ◽  
Xenografted Tumor

Objective. To explore the ability of asiatic acid to interfere with the invasion and proliferation of breast cancer cells by inhibiting WAVE3 expression and activation through the PI3K/AKT signaling pathway. Methods. The MDA-MB-231 cells with strong invasiveness were screened by transwell assay, and plasmids with high expression of WAVE3 were constructed for transfection. The transfection effect and protein expression level of plasmids were verified by PCR and WB. The effects of asiatic acid on cell proliferation and invasion were investigated by flow cytometry. The xenografted tumor models in nude mice were established to study the antitumor activity of asiatic acid. Results. Asiatic acid significantly inhibited the activity of MDA-MB-231 cells, and the expression level of WAVE3 increased significantly in the tissue of ductal carcinoma in situ and was lower than that in the metastasis group. After plasmid transfection, the mRNA and protein expression of WAVE3 increased significantly in the cells. Asiatic acid at different concentrations had an impact on cell apoptosis and invasion and could significantly inhibit the expression of WAVE3, P53, p-PI3K, p-AKT, and other proteins. The T/C(%) of asiatic acid (50 mg/kg) for MDA-MB-231(F10) xenografted tumor in nude mice was 46.33%, with a tumor inhibition rate of 59.55%. Asiatic acid could significantly inhibit the growth of MDA-MB-231 (F10) xenografted tumors in nude mice (p<0.05). Conclusions. Asiatic acid interferes with the ability of breast cancer cells to invade and proliferate by inhibiting WAVE3 expression and activation and the mechanism of action may be related to the PI3K/AKT signaling pathway.

scholarly journals Micronutrients Selenomethionine and Selenocysteine Modulate the Redox Status of MCF-7 Breast Cancer Cells

Nutrients ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 865 ◽  
Author(s):  
Daniel Gabriel Pons ◽  
Carmen Moran ◽  
Marina Alorda-Clara ◽  
Jordi Oliver ◽  
Pilar Roca ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hydrogen Peroxide ◽  
Antioxidant Enzymes ◽  
Protein Expression ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Redox Status ◽  
Hydrogen Peroxide Production ◽  
Low Concentrations ◽  
Mcf 7

Selenium is a micronutrient which is found in many foods, with redox status modulation activity. Our aim was to evaluate the effects of two chemical forms of selenoamino acids, Seleno-L-methionine and Seleno-L-cystine (a diselenide derived from selenocysteine), at different concentrations on cell viability, hydrogen peroxide production, antioxidant enzymes, UCP2 protein expression, as well as lipid and protein oxidative damage in MCF-7 breast cancer cells. Results showed that Seleno-L-methionine did not cause an increase in hydrogen peroxide production at relatively low concentrations, accompanied by a rise in the antioxidant enzymes catalase and MnSOD, and UCP2 protein expression levels. Furthermore, a decrease in protein and lipid oxidative damage was observed at 10 µM concentration. Otherwise, Seleno-L-cystine increased hydrogen peroxide production from relatively low concentrations (100 nM) to a large increase at high concentrations. Moreover, at 10 µM, Seleno-L-cystine decreased UCP2 and MnSOD protein expression. In conclusion, the chemical form of selenoamino acid and their incorporation to selenoproteins could affect the regulation of the breast cancer cell redox status. Taken together, the results obtained in this study imply that it is important to control the type of selenium-enriched nutrient consumption, taking into consideration their composition and concentration.

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