Figure 5.

Tumor progression–dependent changes are seen in Spp1 expression and in other genes in the Spp1 network. (A) The time course of the mean expression level of Spp1, secreted phosphoprotein 1 (better known as osteopontin) in the PC samples of study 1 (left) and study 2 (right). In both studies, the expression of Spp1 in frank tumor cells (days 104/105) was significantly lower (P < .05) than in tumor precursors, regardless which time of tumor induction (days 7-49) was used for t test analysis. (B) Ingenuity pathways analysis (IPA) comparisons of the Spp1-dependent gene network from study 1 on days 7 vs 17 (top row, left), days 7 vs 33 (center), days 7 vs 46 (right) and days 7 vs 104 (bottom row, right). Spp1 and Spp1-regulated target genes are in the center and periphery of network diagrams, respectively. Spp1 targets that were significantly up-regulated when the relatively high Spp1 level on day 7 exhibited further incremental increases (days 17-46) are highlighted in red to the bottom left: Rock2, Cxcl3, Cxcl6, EGFR, MMP9 (P < .001, > 3-fold differences). Spp1 targets that were significantly down-regulated in accordance with the drop in Spp1 levels on day 104 are highlighted in green (P < .001, > 3-fold differences). Note that 3 genes found to be up-regulated in earlier comparisons (Cxcl3, Cxcl6, Rock2) are now found to be significantly down-regulated. Similar results were obtained when the Spp1 network in study 2 was analyzed (not shown).