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The Importance of E7 Oncoprotein Expression in a Mouse Model of HPV Carcinogenesis
Hana Sleiman, Louise Meske, Evie Carchman*
university of Wisconsin, Madison, WI

Introduction: Anal squamous cell carcinoma is a human papillomavirus (HPV) associated cancer, with greater than 90% of anal cancers being positive for one or more high risk genotypes. E6 and E7 are HPV associated oncoproteins that are universally expressed with chronic HPV infections. They are involved in the development of various cancers through their disruption of important tumor suppressor genes, with E6 inhibiting p53 and E7 inhibiting retinoblastoma (pRb). There is little research to date to investigate the effects of E6 alone on anal tumorigenesis versus expression of both E6 and E7 oncoproteins.
Methods: FVB mice expressing only the E6 (K14E6) oncoprotein in their epithelium and mice expressing both E6 and E7 (K14E6/E7) were utilized. There were 28-38 mice per treatment group, per time point (5, 10, 15 and 20 weeks (by 20 weeks of treatment 100% of K14E6/E7 mice have anal tumors)). K14E6 and K14E6/E7 mice were treated with the co-carcinogen DMBA, while control mice were not given treated with any DMBA. All mice were examined on a weekly basis for tumor development and tumors measured. The average number of anal tumors, average anal tumor load (mm), and average total tumor load (including tumors at other sites) (mm) in each group of mice were noted at given time points (5, 10, 15 and 20 weeks). At the time of sacrifice anal tissue was taken and sent for histological analysis. Paired t-test was used to determine diferences between groups.
Results: At 20 and 15 weeks of treatment, there were significant differences (p < 0.0001) in the average number of anal tumors, average anal tumor load, and average total tumor load found in the K14E6 versus K14E6/E7 mice, with K14E6/E7 mice showing higher numbers in all categories. Average differences were not statistically significant enough to prove a distinction in tumor development between K14E6 mice and K14E6/E7 mice at 10 weeks. At five weeks, neither the K14E6 nor the K14E6/E7 mice showed signs of tumor development. K14E6 and K14E6/E7 mice not given DMBA did not develop tumors at any time point. All clinical tumors were confirmed on histology to be squamous cell carcinoma.
Conclusion: E6 alone is not as effective at inducing anal squamous cell carcinoma as compared to mice expressing both the E6 and E7 oncoproteins. These results show that the E7 oncoprotein plays an important role in anal tumorigenesis.


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