Figure 3. Differential transcriptomes of laser capture microdissected mPanIN-like lesions of PK and CPK mice: Validation of differentially expressed Notch1 signaling in CPK.

(a) In vivo expression profile of laser capture microdissected from mPanIN-like lesions of PK and CPK mice (n = 6, each). The heat map represents genes from 2 class t-test p ≤ 0.005 (without multiple testing correction), 191 transcripts with significant upregulation in CPK vs PK were selected. Each row represents log₂ expression ratios of an individual gene and each column indicates an individual sample. Expression ratios are colored according to the scale bar: blue >2-fold downregulation, red >2-fold upregulation. (b) Top 10 functional processes affected by COX-2 overexpression in the PK genetic background. Data analysis among upregulated genes from the 3 months-old CPK and PK gene expression sets resulted in significant enrichment for gene ontology processes related to Notch signaling in development, regulation of lipid metabolism, immune response, cell cycle, survival and apoptosis. (c) Relative gene expression levels of Notch1, Hey1, DLL1, and Hes1 in pancreata of control WT/P/K mice (n = 3) compared to C/CP/CK (n = 3), PK (n = 5) and CPK (n = 5) mice as measured by qRT-PCR. COX-1 amplicons served for normalization. Data is given as mean  ±  SEM. Statistical significance (*p ≤ 0.05, **p ≤ 0.01) was evaluated by Student’s t-test. (d) Expression of Hes1 in pancreata of WT, PK, and CPK mice as detected by immunohistochemistry using anti-Hes-1 antibodies. Note unspecific signals in WT tissue, while nuclear Hes1 signals were observed in TC and mPanIN-like lesions of PK and CPK specimens. Nuclei are stained with hematoxylin. Magnifications: 40x (WT), 63x (PK, CPK).