Profiling of transcripts and proteins modulated by the E7 oncogene in the lung tissue of E7-Tg mice by the omics approach

Abstract

The E6 and E7 oncoproteins of human papilloma virus (HPV) type 16 have been known to cooperatively induce the immortalization and transformation of primary keratinocytes. We established an E7 transgenic mouse model to screen HPV-related biomakers using the omics approach. The methods used to identify HPV-modulated factors were genomics analysis by microarray using the Affymetrix 430 2.0 array to screen E7-modulated genes, and proteomics analysis using nano-LC-ESI-MS/MS to screen E7-modulated proteins with the lung tissue of E7 transgenic mice. According to omics data, cyclin B1, cyclin E2, topoisomerase II·, calnexin, activated leukocyte cell adhesion molecule CD166, actinin ·1, diaphorase 1, gelsolin, platelet glycoprotein, and annexin A2 and A4 were up-regulated in the E7-Tg mice, while proteoglycan 4, sarcolipin, titin, vimentin, drep 1, troponin and cofilin-1 were down-regulated. We further confirmed the significance of differences between the expression levels of the selected factors in E7-Tg and non-Tg mice by real-time PCR. Genes related to cancer cell adhesion, cell cycle and migration, proliferation and apoptosis, as well as to the intermediate filament network and to endoplasmic reticulum proteins, were selected. Taken together, the results suggest that the E7 oncogene modulates the expression levels of cell cycle-related (cyclin B1, cyclin E2) and cell adhesionand migration-related (actinin ·1, CD166) factors, which may play important roles in cellular transformation in cancer. In addition, the solubilization of the rigid intermediate filament network by specific proteolysis mediated via up-regulating gelsolin and down-regulating cofilin-1, as well as increased levels of endoplasmic reticulum protein calnexin with chaperone functions, might also be involved in E7-lung epithelial cells.