ENHANCED DEGRADATION OF P53 PROTEIN IN HPV-6 AND BPV-1 E6-IMMORTALIZED HUMAN MAMMARY EPITHELIAL-CELLS

Normal mammary epithelial cells are efficiently immortalized by the E6 gene of human papillomavirus (HPV)-16, a virus commonly associated wi th cervical cancers. Surprisingly, introduction of the E6 gene from HP V-6, which is rarely found in cervical cancer, or bovine papillomaviru s (BPV)-1, into normal mammary cells resulted in the generation of imm ortal cell tines. The establishment of HPV-6 and BPV-1 E6-immortalized cells was less efficient and required a longer period in comparison t o HPV-16 E6. These HPV-6- and BPV-1 E6-immortalized cells demonstrated dramatically reduced levels of p53 protein by immunoprecipitation. Wh ile the half-life of p53 protein in normal mammary epithelial cells wa s approximately 3 h, it was reduced to approximately 15 min in all the E6-immortalized cells. These results demonstrate that the E6 genes of both high-risk and low-risk papilloma viruses immortalize human mamma ry epithelial cells and induce a marked degradation of p53 protein in vivo.