Cervical Cancer pp 393-406 | Cite as
Generation of K14-E7/∆N87βcat Double Transgenic Mice as a Model of Cervical Cancer
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Abstract
Nearly all cervical cancers are initiated by a subset of high-risk human papilloma viruses (HPVs). However, cervical cancers develop only in a small fraction of women who are infected with these viruses. HPV is required, but not sufficient for developing cervical cancer. Activation of complementary signaling pathways appears to be necessary for malignant transformation of cervical epithelial cells that are immortalized by HPV. Here, we describe the creation and maintenance of a double transgenic mouse model that is based on constitutively active Wnt/β-catenin signaling in cervical epithelial cells expressing the HPV oncoprotein E7. These mice develop invasive cervical squamous carcinomas within 6 months with an average penetrance of 94 %.
Key words
Cervical cancer HPV16 HPV16-E7 Wnt pathway β-catenin K14-E7 transgenic mice K14-∆N87βcat transgenic mice K14-E7/∆N87βcat double transgenic mice K14 promoter Oncogenic β-cateninNotes
Acknowledgement
We wish to thank Drs. Elaine Fuchs for the K14-∆N87βcat mice, Jeffrey Arbeit and Paul Lambert for helpful discussions. We would also like to thank Shannon Fallen, Kevin Chen and Elizabeth L. Drebing for their help in mouse colony maintenance. This study was supported by grants from the National Institutes of Health (NIH) CA108641 (to AU), Cancer Center Support Grant P30 CA051008 for use of Shared Resources (H&E and IHC stainings) and NIH ARRA Grant 1G20 RR025828-01 for use of Rodent Barrier Facility Equipment (between 7/20/2009 and 7/19/2011).
References
- 1.Wolf JK, Franco EL, Arbeit JM et al (2003) Innovations in understanding the biology of cervical cancer. Cancer 98:2064–9PubMedCrossRefGoogle Scholar
- 2.Koutsky LA, Kiviat NB (1999) Genital human papillomavirus. In: Holmes KK, Mardh PA, Sparling PF, et al. (ed) Sexually transmitted diseases, 3rd edn. McGraw Hill, New York, 347–9Google Scholar
- 3.Bulut G, Fallen S, Beauchamp EM et al. (2011) Beta-catenin accelerates human papilloma virus type-16 mediated cervical carcinogenesis in transgenic mice. PLoS One 6(11):e27243. doi: 10.1371/journal.pone.0027243 PubMedCrossRefPubMedCentralGoogle Scholar
- 4.Herber R, Liem A, Pitot H, Lambert PF (1996) Squamous epithelial hyperplasia and carcinoma in mice transgenic for the human papillomavirus type 16 E7 oncogene. J Virol 70:1873–81PubMedPubMedCentralGoogle Scholar
- 5.Gat U, DasGupta R, Degenstein L, Fuchs E (1998) De novo hair follicle morphogenesis and hair tumors in mice expressing a truncated beta-catenin in skin. Cell 95:605–14PubMedCrossRefGoogle Scholar