erbb2 inhibitor ag825  (MedChemExpress)

Journal: Journal of Experimental & Clinical Cancer Research : CR

Article Title: Epidermal growth factor (EGF) receptor-ligand based molecular staging predicts prognosis in head and neck squamous cell carcinoma partly due to deregulated EGF- induced amphiregulin expression

doi: 10.1186/s13046-016-0422-z

Figure Lengend Snippet: EGF and HBEGF induced AREG expression and actuated MAPK and PI3K/Akt pathways in OSCC cell lines. a Both EGF and HBEGF stimulated AREG mRNA expression after two h, peaked at four h and disappeared after 24 h (left panel, Student’s t -test, *** p < 0.001). This was accompanied by increased AREG protein concentration in the supernatant during the following 48 h (right panel; untreated cells were used as control group; Student’s t -test, *** p < 0.001). A representative experiments in the D2 cell line is shown. b EGF induced phosphorylation of the EGF receptor, ERK, p38, JNK, Akt and ErbB2 could be completely inhibited by specific kinase inhibitors. Western blotting from a representative experiment using the D2 cell line

Article Snippet: EGFR inhibitor AG1478 and ErbB2 inhibitor AG825 were obtained from Sigma-Aldrich; MEK inhibitor PD98059, p38 inhibitor SB203580, JNK inhibitor SP600125, and PI3K inhibitor LY294002 were obtained from Calbiochem (Billerica, MA, USA).

Techniques: Expressing, Protein Concentration, Western Blot

Journal: Journal of Experimental & Clinical Cancer Research : CR

Article Title: Epidermal growth factor (EGF) receptor-ligand based molecular staging predicts prognosis in head and neck squamous cell carcinoma partly due to deregulated EGF- induced amphiregulin expression

doi: 10.1186/s13046-016-0422-z

Figure Lengend Snippet: The intracellular pathways in EGF-induced AREG expression. The EGF-induced AREG mRNA ( a ) and protein ( b ) expression was reduced after EGFR-kinase inhibition in all cell lines, while it showed no reduction after ErbB2-kinase inhibition and was differently affected by the MAPK inhibitors. a Whereas MEK-inhibition reduced EGF-induced AREG mRNA expression in all the three cell lines, p38- and JNK-inhibition did not. PI3K-inhibition increased EGF-induced AREG expression in all cell lines. b EGF-induced AREG protein secretion could be totally blocked by EGFR- inhibition. Whereas MEK- and JNK-inhibition profoundly decrease EGF-induced AREG expression in all cell lines, p38-inhibition had no effect. The PI3K-inhibitor reduced EGF-induced AREG production in the conventional OSCC cell line D2 and E10, but had no effect on the basaloid OSSC cell line C12. The ErbB-2- inhibition inhibited the AREG increase in E10 cell line, only. *represents significant difference with EGF stimulation groups without inhibitors (student’s t -test)

Article Snippet: EGFR inhibitor AG1478 and ErbB2 inhibitor AG825 were obtained from Sigma-Aldrich; MEK inhibitor PD98059, p38 inhibitor SB203580, JNK inhibitor SP600125, and PI3K inhibitor LY294002 were obtained from Calbiochem (Billerica, MA, USA).

Techniques: Expressing, Inhibition

Journal: eLife

Article Title: Mechanistic insights into a TIMP3-sensitive pathway constitutively engaged in the regulation of cerebral hemodynamics

doi: 10.7554/eLife.17536

Figure Lengend Snippet: ( A , B ) Schematic representation of the ErbB signaling pathway. Ligands are all produced as membrane-bound precursor proteins that are cleaved by cell-surface sheddases to yield the active growth factor species. Binding of the soluble form of the ligand induces ErbB receptor homodimerization or heterodimerization, converting the receptor to an active dimeric conformation ( A ). Ligands are grouped in four rows according to their receptor specificity (top; arrows); the six ligands for which ectodomain shedding is primarily mediated by ADAM17 appear in black characters, and the remaining five are in grey characters ( B ). ( C – K ) Resting CBF ( C , F , I ) and CBF responses to whisker stimulation ( D , G , J ) or topical application of adenosine ( E , H , K ) were evaluated before and after superfusion of various inhibitors of the ErbB signaling pathway, including the ErbB1/ErbB4 inhibitor AG1478 (10 and 20 µM); the ErbB2 inhibitor AG825 (50 and 200 µM) ( C – E ), the soluble ErbB receptor traps (ErbB1-Fc, 66.7 nM; ErbB3-Fc, 71.4 nM; ErbB4-Fc, 71.4 nM) and the respective control IgG1-Fc and IgG2-Fc fragments (286 nM) ( F – H ), heparin and the synthetic peptide p21 (12 µM) and the control inactive peptide p21-mut (12 µM) ( I – K ). None of these compounds affected resting CBF, except ErbB4-Fc, which produced a slight increase. ( C – K ) Significance was determined by one-way ANOVA followed by Tukey’s post-hoc test (*p<0.05, **p<0.01, ***p<0.001 compared to vehicle; n = 5/group). Error bars indicate SEM. DOI: http://dx.doi.org/10.7554/eLife.17536.015 10.7554/eLife.17536.016 Figure 3—source data 1. Reagents used for . DOI: http://dx.doi.org/10.7554/eLife.17536.016 10.7554/eLife.17536.017 Figure 3—source data 2. Main physiological variables of mice studied in . DOI: http://dx.doi.org/10.7554/eLife.17536.017 10.7554/eLife.17536.018 Figure 3—source data 3. Numerical data that were used to generate the bar charts in . DOI: http://dx.doi.org/10.7554/eLife.17536.018

Article Snippet: Acetylcholine, adenosine, the selective ErbB1/ErbB4 inhibitor tyrphostin AG1478, and the selective ErbB2 inhibitor tyrphostin AG825 ( ) were purchased from Sigma Aldrich (St. Louis, MO).

Techniques: Produced, Binding Assay, Whisker Assay