Journal: Science translational medicine
Article Title: A germline SNP in BRMS1 predisposes patients with lung adenocarcinoma to metastasis and can be ameliorated by targeting c-fos
doi: 10.1126/scitranslmed.abo1050
Figure Lengend Snippet: A) Bar graph showing average invaded cells of H358 cells with shRNAs FOS with or without TCN (10 μg/mL) for 48 h. *P<0.05 compared with the same shRNA FOS–infected WT cells without TCN (control). #P<0.05 and ##P<0.01 compared with the same cell line without TCN. B) H358 cells with shRNA FOS1 were introduced into NSG mice by intracardiac injection. Doxycycline or regular diet was administrated. Bioluminescent images (Left) showing metastases in representative mice at post-injection 1 month and scatter plot (Right) indicating the total bioluminescence (region of interest [ROI]) of each mouse. C) H358 cells were introduced into NSG mice by intracardiac injection, and T5224 or vehicle (control, 20% polyvinylpyrrolidone) was administrated daily 1 month after inoculation. Bioluminescent images (Left) showing metastases in representative mice at post-injection 1 month and scatter plot (Right) displaying the total bioluminescence (ROI) of each mouse. D) PDO-1 and −2 (BRMS1v2A273V/A273V) and PDO-3 and −4 (BRMS1v2WT/WT) were treated with T5224 or DMSO, and 3-D invasion assays performed. The maximal invasion distance (μm) was determined from n=20 PDOs/group. Arrows: the farthest invaded cell.E), F) and G) PDO-1 (BRMS1v2A273V/A273V) or PDO-3 (BRMS1v2WT/WT) was introduced into NSG female mice by intracardiac injection (n=8/group), and T5224 was administrated to mice injected with PDO-1 daily 5 months after inoculation. E) Bioluminescent images (Top) showing metastases in the experimental mice over time and line graph (Bottom) indicating the average total bioluminescence (region of interest [ROI], mean ± S.E.M.) of each mouse at the indicated months post-injection. * comparison between PDO-1 no treatment at post-injection 0.5 month and 5 months, # comparisons between PDO-1 with T5224 treatment and no treatment at post-injection 4 and 5 months, ! comparison between PDO-1 no treatment and PDO-3 no treatment at post-injection 5 months. F) Scatter plots showing the total body weight (left), liver weight (middle) and lung weight (right) of each mouse in both treatment groups at 5 months. G) Hematoxylin and eosin staining of lungs and livers from mice at necropsy. Arrows indicate micrometastases in the lungs.
Article Snippet: The reagents used—c-fos inhibitor T5224 (S8966) and Src inhibitor Saracatinib (AZD0530, S1006)—were purchased from Selleck Chemicals.
Techniques: shRNA, Infection, Control, Injection, Comparison, Staining