Abstract
Infections of human papillomavirus (HPV) induce a variety of benign tumors, such as warts and condylomas. During the process of aberrant cell proliferation, genetic mutations are accumulated in the cells, from which malignant tumor cells arise. The viral oncoproteins E6 and E7 are known to help disrupt the cell cycle checkpoint machinery and accelerate chromosomal instability, events which are critical in malignant conversion. However, the mechanisms involved in the hyperplasia caused by HPV infection have remained unknown. We analysed the effects of regulatory genes of HPV18, a typical high-risk-type HPV, on the formation of the epithelial organ by using an organotypic culture system, and found that E7 had potent activity to induce hyperplasia, to which the disruption of the pRb pathway was well correlated. However, analysis with the E7 variants indicated that other pocket proteins are also involved in the activity.
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Acknowledgements
This work is supported by the Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. TU is supported by Research Fellowships for Young Scientists of the Japanese Society for the Promotion of Science (JSPS). KS and SY are supported by the 21st Century COE Program of JSPS. Full-length clones for HPV18 and HPV11 were provided by Dr Peter M Howley. We thank Dr Akiko Nishimura, Dr Yasutoshi Suzuki, Dr Makoto Tsunenaga and Dr Toshio Kuroki for instructions regarding the organotypic raft culture.
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Ueno, T., Sasaki, K., Yoshida, S. et al. Molecular mechanisms of hyperplasia induction by human papillomavirus E7. Oncogene 25, 4155–4164 (2006). https://doi.org/10.1038/sj.onc.1209445
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DOI: https://doi.org/10.1038/sj.onc.1209445
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