IFN-alfa affects cell cycle progression and induces apoptosis in HPV-positive human cervical carcinoma cells. Studies on E6 gene silenced cells by expression of HPV16-E6 specific siRNA.

Interferon-alfa induces S-phase slowing and cell death in HPV-positive human cervical carcinoma cell lines SiHa and ME-180. These effects appear mediated by PML, a nuclear bodies-associated phosphoprotein, upregulated by IFNs. It is known that PML can induce apoptosis via regulation of p53 acetylation. In these cell lines, where p53 function is inhibited by the HPV E6 oncoprotein, we are setting up a molecular approach of RNA interference technology against HPV oncoproteins to activate a specific interference in the deregulation of cell proliferation due to HPV oncogenic proteins. To date, we sougth to silence HPV-E6 using siRNA to target the specific mRNA. Following a single dose of E6 siRNA treatment of SiHa cells, we observed selective silencing of E6 that induces an increse of the p53 protein. The restored p53 acts by transactivating the cell cycle control gene CDKI-p21, thus suggesting the recovery of cellular regulatory system in these experimental conditions. Interestingly, treatment with IFN alfa of E6 silenced cervical carcinoma cells does not inhibit cell proliferation via cell cycle S-phase slowing and apoptosis induction suggesting that IFN beta induces specific effects on cell cycle in HPV-positive cells that require p53 inhibition by E6 oncoprotein. This result improve the knowledge of signalling mechanism and cell death machinery by which IFN beta can counteract the activity of the oncogenic viral protein E6 in cervical carcinoma cells.