Abstract
Human Papillomavirus cause a number of diseases most notably cervical cancer. K14-HPV16 transgenic mice expressing the HPV16 early genes in squamous epithelial cells provide a suitable experimental model for studying these diseases. MicroRNAs are small non-coding RNAs that play an important role in regulating gene expression and have been suggested to play an important role in cancer development. The role of miR-155 in cancer remains controversial and there is limited evidence linking this miRNA to HPV- associated diseases. We hypothesized that miR-155 expression modulates each tissue’s susceptibility to develop HPV-associated carcinogenesis. In this study, we analyzed miR-155 expression in ear and chest skin samples from 22-26 weeks old, female K14-HPV16 transgenic (HPV16+/-) and wild-type (HPV-/-) mice. Among wild-type mice the expression of miR-155 was lower in ear skin compared with chest skin (p = 0.028). In transgenic animals, in situ carcinoma was present in all ear samples whereas chest tissues only showed epidermal hyperplasia. Furthermore, in hyperplastic chest skin samples, miR-155 expression was lower than in normal chest skin (p = 0,026). These results suggest that miR-155 expression may modulate the microenvironmental susceptibility to cancer development and that high miR155 levels may be protective against the carcinogenesis induced by HPV16.
Highlights
Human papillomaviruses (HPVs) are the most common sexually transmitted agents [1]
The K14-HPV16 transgenic mice develop epidermal hyperplasia that progresses to dysplasia and in situ carcinoma (CIS) lesions and, to invasive cancer
We observed the presence of HPV16 integration in 7 out of 14 animals (Table 2 and Fig. 1)
Summary
The K14-HPV16 transgenic mouse model is useful to study the development of HPV-associated squamous cells carcinomas. In this model, the expression of HPV16 early region genes (E2-E8) is driven by the cytokeratin 14 (K14) promoter/enhancer, targeting epithelial basal cells [5]. The K14-HPV16 transgenic mice develop epidermal hyperplasia that progresses to dysplasia and in situ carcinoma (CIS) lesions and, to invasive cancer. This animal model simulates the multistep carcinogenesis process and facilitates the study of epigenetic and the genetic factors that coordinate malignant conversion and regulate neoplastic progression
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