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. 2012 Mar 12;209(3):437–444. doi: 10.1084/jem.20111923

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© 2012 Cook et al.

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Figure 1. — Notch pathway components are expressed in human and mouse PDA and can be decreased by MRK003. (A) Expression of Notch ligands (DLL4 and Jagged1) and receptor (Notch 3) in mouse (left) and human (right) pancreatic cancer specimens (n = 5 examined). In addition to the expression in PDA neoplastic cells, note expression in endothelial (white arrows) and stromal cells (black arrows). (B) Expression of Notch target genes Hes1 and Hey2 in mouse PanIN and PDA tissue (neoplastic cells marked by black arrows). Hey2 expression is also noted in intratumoral endothelial cells (white arrow; n = 5). (C) In situ hybridization in dark and light fields demonstrating Hes1 expression in pancreatic cancer ductal cells and decreased Hes1 expression upon treatment with MRK003 (GSI; n = 3). (D) Quantitative real-time PCR showing relative mRNA expression of Notch pathway components in PDA tissue from mice treated with vehicle (n = 5) or MRK003 (n = 6) for 10 d. (E) Expression of Hes1 protein in tumors of mice treated with vehicle (n = 8) or GSI (n = 6; **, P = 0.003). Representative images from GSI treated and untreated tumors are shown to the right. Error bars represent SEM. Bars, 100 µm.