Notch signaling pathway mediates different biological processes including stem cell self-renewal, progenitor cell fate decisions, and terminal differentiation. TWIST1 play key roles in tumor development and metastasis through induces epithelial-mesenchymal transition (EMT). Expression of the transcription complex core Notch pathway and target genes, as well as excessive TWIST1, are closely associated with aggressive clinicopathological variables esophageal squamous cell carcinoma (ESCC). Here we aim to explain the possible functional crosstalk between TWIST1 and Notch pathways in ESCCs.
Correlation between TWIST1 and Notch target genes was analyzed in 50 ESCCs and corresponding normal tissue. Using retroviral system, forced expression TWIST1 established ESCC KYSE-30 cell line and the expression of genes Notch signaling was assessed. a significant correlation between the expression TWIST1 and HEY1 / by hey2 found in different pathological variables of ESCC poor prognosis.
TWIST1 induced expression in KYSE-30 cells led to an increase noteworthy of Notch pathway gene expression revealed TWIST1 gene regulatory role of Notch signaling in cells. Based on the existing correlation between the expression of genes TWIST1 and Notch pathway in different pathological features of patients with ESCC, and KYSE-30 cell line, we can estimate that TWIST1 involved in the aggressiveness of the disease through regulation of Notch signaling genes. To the best of knowledge, this is the first report describing the effect TWIST1 Notch cascade genes in ESCC
TWIST1 correlates with Notch signaling pathway to develop esophageal squamous cell carcinoma
3-O- (E) p-Coumaroyl betulinic acid has anti-cancer activity and inhibits the Notch signaling pathway in breast cancer cells and mammosphere
Activation of Notch signaling is associated with tumor aggressiveness, poor clinical outcomes and drug resistance in breast cancer patients. Targeting Notch signaling with small molecule inhibitors may be a better strategy for anticancer drug development. We identified 3-O- (E) p-Coumaroylbetulinic acid (CB) as a lead compound and a potent inhibitor of Notch signaling pathway. Treatment of human breast cancer MBA-MD-231 and T47D cells with CB resulted in dose-and time-dependent inhibition of cell viability and G0 / G1 phase cell cycle arrest.
This effect was associated with a sharp decrease in the expression of cyclin D1 and its activating partner, cyclin-dependent kinase 2 with a concomitant increase in the cyclin kinase inhibitor p21, operating in G1 phase of the cell cycle. CB treatment induced early apoptosis of breast cancer cells as evidenced by an increase in cleaved caspase-3, a decrease in Bcl-2 and survivin, a surge of reactive oxygen species and mitochondrial membrane potential interference. CB treatment Notch target gene is altered.
Hes1, Hey1 and E-cadherin at the mRNA and protein levels in a time-dependent manner along with a decrease in Notch promoter activity at IC50 concentrations. Furthermore, treatment CB decline mammosphere formation in MCF-7 cells by down-modulation of the Notch signaling pathway and suppression of self-renewal markers such as c-Myc, SOX-2 and CD44. Our findings indicate that the CB has anticancer activity in breast cancer cells and suppress the ability of self-renewal in mammosphere as a result of modulation of cell-cycle engine, impaired mitochondrial function, induction of apoptosis, and inhibition.
Description: The Notch CSL Reporter andndash; HEK293 cell line contains the firefly luciferase gene under the control of Notch-response elements (CSL responsive elements) alone with expression construct for Notch1 E (NOTCH1 that has a deletion of the entire extracellular domain) stably integrated into HEK293 cells. Inside the cells, the Notch1 E can be cleaved by andgamma;-secretase. The active Notch1 NICD is released to nucleus and induces the constitutive expression of luciferase reporter. The cell line is validated for the inhibition of the expression of luciferase reporter using a known inhibitor of the Notch signaling pathway.
Human Notch Signaling Pathway Notch1/CSL Reporter Cell Line-HEK293
Description: Human Notch Signaling Pathway Notch1/CSL Reporter Cell Line is derived from HEK293. Application: • Monitor Notch signaling pathway activity.• Screen for activators or inhibitors of the Notch signaling pathway.
Description: The Notch1/CSL Transient Packis designed to provide the tools necessary for transiently transfecting and monitoring the activity of the Notch signaling pathway in HEK293 cultured cells. The kit contains transfection-ready vectors containing firefly luciferase as a Notch pathway-responsive reporter and constitutively expressing Renilla luciferase as a transfection control. It also includes the Dual Luciferase detection reagents to detect both luciferase activities and specialized medium for growing and assaying HEK293 cells._x000D_The key to the Notch1/CSL Transient Pack is the expression vector for NOTCH1 that has a deletion of the entire extracellular domain (Notch1DE). Inside the cells, the NOTCH1 DE can be cleaved by γ-secretase and active NOTCH1 NICD is released into the nucleus. The kit also contains CSL (CBF1/RBP-Jk) luciferase reporter vector, which is a Notch pathway-responsive reporter. This reporter contains the firefly luciferase gene under the control of multimerized CSL responsive elements upstream of a minimal promoter. The CSL (CBF1/RBP-Jk) reporter is premixed with constitutively expressing Renilla (sea pansy) luciferase vector, which serves as an internal positive control for transfection efficiency._x000D_The pack also includes a non-inducible firefly luciferase vector premixed with constitutively-expressing Renilla luciferase vector as a negative control. The non-inducible luciferase vector contains a firefly luciferase gene under the control of a minimal promoter, but without any additional response elements. The negative control is critical for determining pathway specific effects and background luciferase activity._x000D_Additionally, the pack includes cell culture medium (BPS Medium 1) that has been optimized for use with HEK293 cells*. BPS Medium 1 includes MEM medium, 10% fetal bovine serum, 1% non-essential amino acids, sodium pyruvate, and 1% Pen/Strep. Finally, the pack provides the Dual Luciferase (Firefly-Renilla) Assay System. These luciferase reagents provide highly sensitive, stable detection of firefly luciferase activity and Renilla luciferase activity. The dual luciferase reagents can be used directly in cells in growth medium, and can be detected with any luminometer; automated injectors are not required. _x000D_*Note: the kit may be used with other cell lines than HEK293, but an alternate cell culture medium may be required for optimal cell growth,
Description: A competitive ELISA for quantitative measurement of Rat Agouti signaling protein(ASIP) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rat Agouti signaling protein(ASIP) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rat Agouti signaling protein(ASIP) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A sandwich ELISA for quantitative measurement of Rat Suppressors Of Cytokine Signaling 3 in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A sandwich ELISA for quantitative measurement of Rat Suppressors Of Cytokine Signaling 3 in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A sandwich ELISA for quantitative measurement of Rat Suppressors Of Cytokine Signaling 3 in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rat Suppressors Of Cytokine Signaling 1 in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rat Suppressors Of Cytokine Signaling 1 in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rat Suppressors Of Cytokine Signaling 1 in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rat Regulator Of G Protein Signaling 4 in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rat Regulator Of G Protein Signaling 4 in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rat Regulator Of G Protein Signaling 4 in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Inhibiting Notch Notch signaling may be an effective way to prevent retinal fibrosis , This study is of clinical significance in developing treatments to prevent fibrosis in proliferative vitreoretinopathy, proliferative diabetic retinopathy and wet age-related macular degeneration.
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