Novel ß-HPV49 Transgenic Mouse Model of Upper Digestive Tract Cancer

Area of Science:

• Oncology
• Virology
• Carcinogenesis

Background:

• The beta genus of human papillomaviruses (ß-HPV) comprises about 50 types, with limited understanding of most types' biology and disease links.
• While some ß-1 and ß-2 HPV types are implicated in nonmelanoma cancers, the role of other ß-HPV types remains largely uncharacterized.

Purpose of the Study:

• To investigate the oncogenic potential of the ß-3 type HPV49 E6 and E7 genes in a transgenic mouse model.
• To compare the carcinogenic effects of HPV49 with HPV38 in different anatomical sites and in response to distinct carcinogens.

Main Methods:

• Generation of K14 HPV49 E6/E7-Tg mice expressing viral oncogenes in skin and digestive tract epithelia.
• Assessment of spontaneous tumor formation, proliferation, and susceptibility to 4-nitroquinoline 1-oxide (4NQO) or UV irradiation.

Main Results:

• K14 HPV49 E6/E7-Tg mice showed minimal epidermal proliferation and no spontaneous tumors but were highly susceptible to 4NQO-induced upper digestive tract cancer.
• These mice were resistant to UV-induced skin carcinogenesis.
• An analogous K14 HPV38 E6/E7-Tg model showed susceptibility to UV-induced skin cancer but not 4NQO-induced digestive tract cancer.

Conclusions:

• Beta-HPV types exhibit distinct oncogenic properties influencing carcinogenesis in a site-specific manner.
• HPV49 primarily contributes to digestive tract carcinogenesis, while HPV38 is linked to skin carcinogenesis.