Apoptosis and cell growth genes are regulated in an SHC1-dependent manner. (A) HeLa cells were infected for 4 h (C. trachomatis L2, MOI 20) before RNA isolation and array hybridization. Gene expression profiles of infected versus noninfected cells (Inf (vs. NI)) were compared with infected SHC1 knockdown versus infected Luciferase knockdown cells (SHC1 KD + Inf (vs. Luci KD + Inf)) to determine infection and SHC1-dependently regulated genes (n = 2, each with dye swap). In total, 21 genes are regulated in both a SHC1- and infection-dependent manner (up-regulated genes are shown in red, down-regulated genes in green). (B) The 21 genes that correlate with both infection and SHC1 signaling were further analyzed using the IPA software. Of these, eight genes are grouped into the functional category “apoptosis” and another eight genes are assigned to the category “cell growth.” (C) Gene enrichment analysis of the overlapping genes (21) compared with all regulated genes (610). Both functional categories “apoptosis” and “cell growth” are significantly enriched in the 21 overlapping genes (as determined by Fisher’s exact test). (D) Model of the role of SHC1 during early infection-mediated gene regulation. C. trachomatis activates SHC1 leading to four groups of regulated genes. Expression of group 1 genes is likely inhibited by SHC1 activation, explaining their up-regulation after SHC1 knockdown in infected cells. In contrast, gene expression in group 3 is likely enhanced by SHC1 activation, causing a down-regulation of group 3 genes after SHC1 knockdown in infected cells. Genes of groups 2 and 4 show an additional regulation by C. trachomatis infection independent of SHC1, which remains after SHC1 knockdown in infected cells.