Transcription profiling of mouse ervical and skin tissues from HPV 16 E6 transgenic animals

ABSTRACT: Background; The in vivo properties of HR-HPV E6 and E7 oncoproteins have been previously evaluated through the generation and characterization of HPV transgenic mouse strains. Although K14E6 transgenic mice develop spontaneous tumors of the skin epithelium, no spontaneous reproductive tract malignancies arise, unless the transgenic mice were treated chronically with 17β-estradiol. Taken together, these findings suggest that E6 performs critical functions in normal adult cervix and skin, highlighting the need to define E6-controlled transcriptional programs in these tissues. We evaluated the different expression profile of 14,000 genes in skin or cervix from young K14E6 transgenic mice compared with corresponding tissues from non-transgenic (FVB) mice. Result; Microarray analysis identified a total of 676 and 1154 genes that were significantly up and down-regulated, respectively, in skin from K14E6 transgenic mice. On the other hand, in cervix from K14E6 transgenic mice we found that only 97 and 252 genes were significantly up and down-regulated, respectively. One of the most affected processes in the skin from K14E6 transgenic mice was the cell cycle. We also found that skin from transgenic mice showed down-regulation in pro-apoptotic genes expression, particularly in those related to the extrinsic apoptotic pathway. In contrast, we observed up-regulation of anti-apoptotic genes. Another pathway that was severely affected in skin was the immune response. In cervix from transgenic mice, we could not find affected any gene related to the cell cycle and apoptosis pathways. Interestingly, we observed alterations in the expression of immune response genes in cervix from K14E6 transgenic mice. Pathways such as angiogenesis, cell junction, cytoskeleton, keratinocyte differentiation and epidermis development, showed different gene expression in skin or cervix from K14E6 transgenic mice. Conclusion; Alterations in gene expression identified in the current study might partially explain why our K14E6 transgenic mice present a more aggressive phenotype in the skin than in the cervix. Expression of the HPV16 E6 oncoprotein alters expression of genes that fell into several functional groups providing insights into pathways by which E6 deregulate cell cycle progression, apoptosis and the host resistance to infection and immune function, providing new opportunities for early diagnostic markers and therapeutic drug targets. Experiment Overall Design: We compared the expression paterns in the skin and cervix of K14E6 transgenic mice against the same tissues from non-transgenic FVB mice. For each tissue, we pooled total RNA from three different 6 week virgin mice. Total RNA from the cervix and lower reproductive tract and dorsal skin were obtained from fresh frozen tissue using Trizol. Total RNA was processed an hybridized onto Affymetrix Mouse Genome 430A 2.0 Arrays. For each sample, a technical replica was included.

ORGANISM(S): Mus musculus

SUBMITTER: Alfredo Hidalgo-Miranda 

PROVIDER: E-GEOD-10702 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress