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. Author manuscript; available in PMC: 2020 Aug 1.
Published in final edited form as: Mol Cancer Res. 2019 May 14;17(8):1639–1651. doi: 10.1158/1541-7786.MCR-18-1292

Figure 5. Overexpression of Nodal in TSC-associated renal tumors.

Figure 5.

(A) (i) Hematoxylin and eosin staining in angiomyolipoma tumors from three TSC patients; (second to fifth panels) Expression of Nodal in (ii) TSC-associated angiomyolipomas, (iii) non-diseased normal kidneys, (iv) sporadic angiomyolipoma, (v) LAM by (ii) immunofluorescence and (iii-v) immunohistochemistry, scale bars 50μm.

(B-C) Expression of (B-i-ii) Notch1 and (B-i, B-iii, C) Nodal in (B-i) sporadic human RCC (from Human Protein Atlas), (B-ii-iii, C) kidneys (NestinCre;p53f/+ and NestinCre;Tsc1f/+) and/or RCC (NestinCre;Tsc1f/+;p53f/+ and NestinCre;Tsc1f/+;p53f/f), by (B-ii-iii) q(RT)-PCR relative to GAPDH, (C-i-ii) immunohistochemistry (arrows indicate renal carcinoma, arrowheads indicate normal kidney); scale bars 50μm. (C-iii) The correlation between the percentage of area with strong expression of Nodal (Aperio-Digital Pathology) and mouse age. (C-iv) The correlation between the percentage of area expressing Nodal and p53 status and mouse age.

(D) Binding of Notch1 to the NODAL promoter to two NRE sites (N1 and N2) by ChIP-qPCR in NestinCre;p53f/+, NestinCre;Tsc1f/+, NestinCre;Tsc1f/+;p53f/+ mice shown as fold enrichment over the IgG (dotted line).

Data represent means±SEM. *P≤0.05, **P≤0.01, ***P≤0.001, ****P≤0.0001.

Data are representative of five (A), n=19, n=14 animals (B-ii-iii), n=65 (C), n=7 (D) independent experiments.