Fig. 5

HER2 expression primes cells for hypoxia in MCF7-HER2 cells. Rank product testing of gene expression data (FDR = 0.05) was used to identify genes which were significantly induced in hypoxia (performed separately for acute and chronic) in each cell line and compared to genes significantly more highly expressed in either of the cell lines (A). The number of genes belonging into each category is shown in the centre of each pie chart, with the proportion of those genes represented by HIF-1, HIF-2 or HIF-1/HIF-2 target genes shown in green red or blue, respectively. Notably, a larger proportion of HIF target genes are present in hypoxic response unique to MCF7-HER2 when compared to the unique MCF7 response in acute and chronic hypoxia. Additionally, a relatively large proportion of genes which can be induced by hypoxia are constitutively increased by in MCF7-HER2, with little or no equivalent set constitutively upregulated in MCF7. This suggests that HER2 overexpression can prepare the cells for hypoxia with the normoxic expression of both HIF-regulated and non-HIF hypoxia response genes. Hypoxia response genes constitutively upregulated in MCF7-HER2 (primed genes) and genes involved in the hypoxic response in MCF7-HER2 only (HER2-specific genes) contain a number of pathologically interesting genes involved in a number of important cellular processes (B)