1. ¹International Agency for Research on Cancer, World Health Organization, Infections and Cancer Biology Group, Lyon, France
2. ²INSERM, U851, Lyon, France
3. ³IFR128, BioSciences Lyon-Gerland, Lyon, France
4. ⁴Université Lyon 1, Villeurbanne, France
5. ⁵Deutsches Krebsforschungszentrum, Heidelberg, Germany

Correspondence: Dr M Tommasino, Infections and Cancer Biology Group, International Agency for Research on Cancer, World Health Organization, Lyon 69008, France. E-mail: tommasino@iarc.fr

Received 18 June 2007; Revised 18 September 2007; Accepted 22 October 2007; Published online 19 November 2007.

Abstract

We have previously shown that human keratinocytes expressing E6 and E7 from the cutaneous human papillomavirus (HPV) type 38 have high levels of a specific form of p53, which in turn activate the transcription of Np73 gene. Expression of HPV38 E6 and E7 in mouse skin also promotes p53 and Np73 accumulation. Interestingly, keratinocytes of these mice do not undergo cell cycle arrest after skin ultraviolet (UV) irradiation. Here, we provide several lines of evidence that Np73 expression and lack of the UV response are directly linked. Loss of p53 gene in HPV38 E6/E7 transgenic mice abolished Np73 expression and partially restored the UV-activated cell cycle checkpoints. Similarly, loss of p73, and consequently Np73, led to restoration of the p53 pathways. In fact, keratinocytes of p73^{- /-} HPV38 E6/E7 transgenic mice upon UV irradiation express high levels of p21^WAF1 and are cell cycle arrested. Thus, HPV38 E6 and E7, via Np73 accumulation, are able to alter the regulation of cell cycle checkpoints activated by UV radiation. These data suggest that UV and HPV may cooperate in skin carcinogenesis.