Altamura Gennaro, Corteggio Annunziata, Pacini Laura, Conte Andrea, Pierantoni Giovanna Maria, Tommasino Massimo, Accardi Rosita, Borzacchiello Giuseppe
Department of Veterinary Medicine and Animal Productions, General Pathology and Pathological Anatomy Unit, University of Naples Federico II, Via Delpino 1, 80137 Naples, Italy.
Infections and Cancer Biology Group, International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372 Lyon, France.
Virology. 2016 Sep;496:1-8. doi: 10.1016/j.virol.2016.05.017. Epub 2016 May 26.
Felis catus papillomavirus type 2 (FcaPV2) DNA is found in feline cutaneous squamous cell carcinomas (SCCs); however, its biological properties are still uncharacterized. In this study, we successfully expressed FcaPV2 E6 and E7 putative oncogenes in feline epithelial cells and demonstrated that FcaPV2 E6 binds to p53, impairing its protein level. In addition, E6 and E7 inhibited ultraviolet B (UVB)-triggered accumulation of p53, p21 and pro-apoptotic markers such as Cleaved Caspase3, Bax and Bak, suggesting a synergistic action of the virus with UV exposure in tumour pathogenesis. Furthermore, FcaPV2 E7 bound to feline pRb and impaired pRb levels, resulting in upregulation of the downstream pro-proliferative genes Cyclin A and Cdc2. Importantly, we demonstrated mRNA expression of FcaPV2 E2, E6 and E7 in feline SCC samples, strengthening the hypothesis of a causative role in the development of feline SCC.
在猫皮肤鳞状细胞癌(SCC)中发现了猫乳头瘤病毒2型(FcaPV2)DNA;然而,其生物学特性仍未明确。在本研究中,我们成功地在猫上皮细胞中表达了FcaPV2 E6和E7推定癌基因,并证明FcaPV2 E6与p53结合,损害其蛋白水平。此外,E6和E7抑制紫外线B(UVB)触发的p53、p21和促凋亡标志物(如裂解的Caspase3、Bax和Bak)的积累,表明该病毒与紫外线暴露在肿瘤发病机制中具有协同作用。此外,FcaPV2 E7与猫pRb结合并损害pRb水平,导致下游促增殖基因细胞周期蛋白A和细胞周期蛋白依赖性激酶2(Cdc2)上调。重要的是,我们证明了FcaPV2 E2、E6和E7在猫SCC样本中的mRNA表达,强化了其在猫SCC发生中起致病作用的假说。