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. 2021 Apr 6;10:e66788. doi: 10.7554/eLife.66788

Figure 3. NKX2-1 regulates MAPK pathway in BRAFV600E-driven LUAD.

(A, B) IHC for indicated proteins in lung neoplasia present at 8 weeks post-initiation in BrafLSL-V600E/+;Trp53f/f;Nkx2-1f/+;Rosa26LSL-tdTomato/LSL-tdTomato and BrafLSL-V600E/+;Trp53f/f;Nkx2-1f/f;Rosa26LSL-tdTomato/LSL-tdTomato mice. (C) IHC quantitation of phosphoproteins in indicated tumor types (n = 2–4 mice/genotype). Each dot represents one tumor. Error bars indicate mean ± S.D. ****p<0.0001, ***p<0.001, ns = not significant by Mann-Whitney test. (D) Representative staining of phospho-ERK in human non-mucinous (NKX2-1-positive, n = 51) and mucinous (NKX2-1-negative, n = 17) lung tumors. Scale bar: 500 µm.

Figure 3.

Figure 3—figure supplement 1. NKX2-1 regulates MAPK pathway in BRAFV600E-driven LUAD.

Figure 3—figure supplement 1.

(A) IHC for indicated phospho-proteins in NKX2-1-positive and -negative LUADs. Lung tumor sections were obtained from corn oil or tamoxifen-treated BrafFSF-V600E/+;Trp53frt/frt;Nkx2-1f/f;Rosa26FSF-CreERT2/FSF-CreERT2 mice 6 weeks post-initiation with Ad5CMV-FlpO. (B) IHC quantitation of phosphoproteins in indicated tumor types. Error bars indicate mean ± S.D. ****p<0.0001, ***p<0.001, *p<0.05 by Mann-Whitney test. At least 10 tumors across 2–3 mice were analyzed. (C) Long-term 3D cultures of primary mouse LUAD cells isolated from BrafLSL-V600E/+;Trp53f/f;Nkx2-1f/+;Rosa26LSL-tdTomato/LSL-tdTomato (BP) and BrafLSL-V600E/+;Trp53f/f;Nkx2-1f/f;Rosa26LSL-tdTomato/LSL-tdTomato (BPN) mice 8 weeks post-initiation. Shown are representative IHC photomicrographs. Scale bar: 100 µm. (D) Quantitation of phospho-ERK levels in human lung tumors relative to NKX2-1 expression/histologic subtype.