Loss of p53 protein in human papillomavirus type 16 E6-immortalized human mammary epithelial cells.
We have shown previously that introduction of the human papillomavirus type 16 (HPV16) or HPV18 genome into human mammary epithelial cells induces their immortalization. These immortalized cells have reduced growth factor requirements. We report here that transfection with a single HPV16 gene E6 is sufficient to immortalize these cells and reduce their growth factor requirements. The RB protein is normal in these cells, but the p53 protein is sharply reduced, as shown by immunoprecipitation with anti-p53 antibody (pAB 421). We infer that the E6 protein reduces the p53 protein perhaps by signalling its destruction by the ubiquitin system. The HPV-transforming gene E7 was unable to immortalize human mammary epithelial cells. Thus, cell-specific factors may determine which viral oncogene plays a major role in oncogenesis.
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Division of Cancer Genetics, Dana-Farber Cancer Institute, Boston, Massachusetts 02115.
De Caprio
J A
JA
Delmolino
L
L
Kulesa
V
V
Sager
R
R
D015153:Blotting, Western; D001940:Breast / Q000166:cytology / Q000382:microbiology / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004847:Epithelial Cells; D004848:Epithelium / Q000502:physiology; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D009856:Oncogene Proteins, Viral / Q000235:genetics; D027383:Papillomaviridae / Q000235:genetics*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics; D012097:Repressor Proteins; D016160:Retinoblastoma Protein / Q000032:analysis; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000235:genetics*
C068651:E6 protein, Human papillomavirus type 16; D007328:Insulin; D009856:Oncogene Proteins, Viral; D012333:RNA, Messenger; D012097:Repressor Proteins; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D004815:Epidermal Growth Factor; D006854:Hydrocortisone