Journal: Nature Communications
Article Title: Sustained activation of the Aryl hydrocarbon Receptor transcription factor promotes resistance to BRAF-inhibitors in melanoma
doi: 10.1038/s41467-018-06951-2
Figure Lengend Snippet: Long-term canonical activation of AhR drives melanoma resistance to BRAFi. a Graphical representation of AhR function controlling melanoma cell sensitivity or resistance during BRAFi treatment. A high level of heterogeneity is observed among melanomas with a high proportion of highly differentiated and β-cells sensitive to BRAFi (induction of pigmentation by AhR: β signature) and a weak number of undifferentiated and α-cells resistant to BRAFi (induction of α signature and resistance genes). These persister cells constitute a cell reservoir leading to melanoma relapse. b Graphical model of AhR activation by BRAFi and α-ligands, with α-ligands dictating melanoma resistance. c Expression heatmap for resistant genes in 501Mel cells treated for 7–14 days with TCDD (10 nM). d 501 melanoma cells (501Mel) were pre-treated daily or not for 2 weeks with TCDD (10 nM) and treated 4 days with increasing concentrations of Vem in order to establish cell density measurements and calculate IC50 (sensitivity to Vem). Values, calculated with GraphPad (PRISM6.0 ® ), represent the IC50 of Vem for control cells (without TCDD pre-treatment) or after 2 weeks of TCDD. e Expression heatmap for β-, α-, and resistance genes in 501Mel cells invalidated or not for AhR by CRISPR/Cas9 before or 48 h after treatment with Vem (1 μM). f Expression Heatmap for β-, α-, and resistance genes in 501Mel and SKMEL28 (R) cells knocked-down for AhR or ARNT using siRNA. The human silhouettes have been adapted (change of color background) from Servier Medical Art, licensed under a CC BY 3.0 FR [ https://smart.servier.com/smart_image/shape-29/ ]
Article Snippet: Plasmids encoding shRNA targeting human AhR (TL320259, 29mer shRNA constructs in lentiviral GFP vector) were purchased from Origene, Rockville, MD.
Techniques: Activation Assay, Expressing, CRISPR
OriGene is a verified supplier 
OriGene manufactures this product 
![Long-term canonical activation of <t>AhR</t> drives melanoma resistance to BRAFi. a Graphical representation of AhR function controlling melanoma cell sensitivity or resistance during BRAFi treatment. A high level of heterogeneity is observed among melanomas with a high proportion of highly differentiated and β-cells sensitive to BRAFi (induction of pigmentation by AhR: β signature) and a weak number of undifferentiated and α-cells resistant to BRAFi (induction of α signature and resistance genes). These persister cells constitute a cell reservoir leading to melanoma relapse. b Graphical model of AhR activation by BRAFi and α-ligands, with α-ligands dictating melanoma resistance. c Expression heatmap for resistant genes in 501Mel cells treated for 7–14 days with TCDD (10 nM). d 501 melanoma cells (501Mel) were pre-treated daily or not for 2 weeks with TCDD (10 nM) and treated 4 days with increasing concentrations of Vem in order to establish cell density measurements and calculate IC50 (sensitivity to Vem). Values, calculated with GraphPad (PRISM6.0 ® ), represent the IC50 of Vem for control cells (without TCDD pre-treatment) or after 2 weeks of TCDD. e Expression heatmap for β-, α-, and resistance genes in 501Mel cells invalidated or not for AhR by CRISPR/Cas9 before or 48 h after treatment with Vem (1 μM). f Expression Heatmap for β-, α-, and resistance genes in 501Mel and SKMEL28 (R) cells knocked-down for AhR or ARNT using siRNA. The human silhouettes have been adapted (change of color background) from Servier Medical Art, licensed under a CC BY 3.0 FR [ https://smart.servier.com/smart_image/shape-29/ ]](https://pub-med-central-images-cdn.bioz.com/pub_med_central_ids_ending_with_5830/pmc06235830/pmc06235830__41467_2018_6951_Fig5_HTML.jpg)