Differential gene expression between skin and cervix induced by the E7 oncoprotein in a transgenic mouse model

HPV16 E7 oncoprotein expression in K14E7 transgenic mice induces cervical cancer after 6 months of treatment with the co-carcinogen 17β-estradiol. In untreated mice, E7 also induces skin tumors late in life, albeit at low penetrance. These findings indicate that E7 alters cellular functions in cervix and skin so as to predispose these organs to tumorigenesis. Using microarrays, we determined the global genes expression profile in cervical and skin tissue of young adult K14E7 transgenic mice without estrogen treatment. In these tissues, the E7 oncoprotein altered the transcriptional pattern of genes involved in several biological processes, including immune response, intracellular signaling cascades, cell adhesion, cell migration, development, cell cycle, growth, response to wounding and regulation of apoptosis. Among the E7-dysregulated genes were ones not previously known to be involved in cervical neoplasia, including DMBT1, GLI1 and 17βHSD2 in cervix and MMP2, 12, 14, 19 and 27 in skin. The experiment consists of a total of 24 samples to evaluate the mRNA expression profiles in 4 different groups: skin biopsy of transgenic mice K14E7, cervix biopsy of transgenic mice K14E7, skin biopsy of FVB/N control virgin mice and cervix biopsy of FVB/N control virgin mice. Each group has 6 samples that had been processed in 3 pools of two samples (biological replicates) for a total of 6 samples for each condition.