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 with cervical cancers. Surprisingly, introduction of the E6 gene from HPV-6, which is rarely found in cervical cancer, or bovine papillomavirus (BPV)-1, into normal mammary cells resulted in the generation of immortal cell lines. The establishment of HPV-6 and BPV-1 E6-immortalized cells was less efficient and required a longer period in comparison to HPV-16 E6. These HPV-6- and BPV-1 E6-immortalized cells demonstrated dramatically reduced levels of p53 protein by immunoprecipitation. While the half-life of p53 protein in normal mammary epithelial cells was 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 mammary epithelial cells and induce a marked degradation of p53 protein in vivo.
Department of Radiation Oncology, New England Medical Center Hospitals, Boston, MA.
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D001483:Base Sequence; D001940:Breast / Q000166:cytology / Q000378:metabolism*; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D004268:DNA-Binding Proteins; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D005814:Genes, Viral; D006207:Half-Life; D006801:Humans; D008969:Molecular Sequence Data; D009841:Oligonucleotides; D009856:Oncogene Proteins, Viral / Q000235:genetics; D027383:Papillomaviridae / Q000235:genetics / Q000502:physiology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; C068651:E6 protein, Human papillomavirus type 16; C052603:E6 protein, Human papillomavirus type 18; D009841:Oligonucleotides; D009856:Oncogene Proteins, Viral; D012333:RNA, Messenger; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53; C059269:protein E6, Bovine papillomavirus