Figure 6

Time profiles for selected early (A), delayed (B) and late (C) genes differentially expressed in transiently versus sustained gastrin treated cells. The panels show data from three independent time series microarray experiments. Left panels: mRNA expression level (normalized log2-transformed signal intensities) for untreated (open dots) and sustained gastrin treated (black dots) cells. Experimental protocol is described in the legend to Figure 2B. Middle panels: Gastrin induced gene expression in transiently (grey lines) and sustained (black lines) treated cells. The data is shown as mean fold induction relative to untreated cells at the same time point (N=2; see Figure 1A for details). Right panels: The effect of sustained gastrin treatment was measured in the presence (grey lines) and absence (black lines) of cycloheximide (CHX). The data is shown as mean fold induction relative to either untreated cells (gastrin versus untreated) or relative to CHX treated cells (gastrin and CHX versus CHX) at the same time point (1-10 h). The early primary genes c-Fos and Junb as well as the delayed primary gene Hdac5 are super-induced in the presence of CHX. Thus, these genes are probably repressed by other gastrin-induced repressors dependent on de novo protein synthesis [37]. The late gene Maged2 is a primary gene. The delayed gene Vegfa and the late genes Prss1 and Prss3 (LOC362347) are secondary. Hdac5 is a co-transcription factor involved in histone modification and shown to control cell-cycle progression and survival of human cancer cells [45]. VEGFA acts on endothelial cells and has various effects, including mediating increased vascular permeability, inducing angiogenesis and cell growth, promoting cell migration, and inhibiting apoptosis [46]. Maged2 has been classified as a co-transcription factor and are found elevated in e.g., goblet cell adenocarcinoids compared to normal mucosa [47]. Prss1 and Prss3 are discussed in the main text.