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The E7 open reading frame of human papillomavirus type 16 encodes a transforming gene. 1988

K H Vousden, and J Doniger, and J A DiPaolo, and D R Lowy
Laboratory of Cellular Oncology, National Cancer Institute, Bethesda, Maryland 20892.

Prior analysis of bovine papillomavirus has identified two genes, E5 and E6, which induce morphologic transformation of certain established cells. To study the transforming genes of human papillomavirus (HPV) type 16, the HPV type most commonly associated with cervical carcinoma, we examined subgenomic viral DNAs under control of a retroviral long terminal repeat for their capacity to induce cellular transformation of NIH 3T3 cells. Plasmids carrying the entire viral early region, the E6 and E7 (E6/E7) open reading frames (ORFs), or the E2,E4, and E5 (E2-E5) ORFs induced a very low frequency of focal transformation (0.4-1.7 ffu/micrograms DNA). In contrast, the plasmids with the entire early region of E6/E7, when selected by co-transfection with a transformation independent marker (neoR), induced anchorage independent growth with high efficiency. Cells selected after co-transfection with the marker gene and the E2-E5 plasmid grew much less efficiently in agar. Mutational analysis of the E6/E7 plasmid indicated that E7 was the gene primarily responsible for inducing anchorage independent growth. E7 gene therefore represents a third class of PV transforming gene. These results correlate with E7 (along with E6) being selectively retained and expressed in HPV associated cervical carcinomas and cell lines.

UI MeSH Term Description Entries
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D009856 Oncogene Proteins, Viral Products of viral oncogenes, most commonly retroviral oncogenes. They usually have transforming and often protein kinase activities. Viral Oncogene Proteins,Viral Transforming Proteins,v-onc Proteins,Transforming Proteins, Viral,v onc Proteins
D010957 Plasmids Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS. Episomes,Episome,Plasmid
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D002472 Cell Transformation, Viral An inheritable change in cells manifested by changes in cell division and growth and alterations in cell surface properties. It is induced by infection with a transforming virus. Transformation, Viral Cell,Viral Cell Transformation,Cell Transformations, Viral,Transformations, Viral Cell,Viral Cell Transformations
D004268 DNA-Binding Proteins Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases. DNA Helix Destabilizing Proteins,DNA-Binding Protein,Single-Stranded DNA Binding Proteins,DNA Binding Protein,DNA Single-Stranded Binding Protein,SS DNA BP,Single-Stranded DNA-Binding Protein,Binding Protein, DNA,DNA Binding Proteins,DNA Single Stranded Binding Protein,DNA-Binding Protein, Single-Stranded,Protein, DNA-Binding,Single Stranded DNA Binding Protein,Single Stranded DNA Binding Proteins
D004279 DNA, Viral Deoxyribonucleic acid that makes up the genetic material of viruses. Viral DNA
D005814 Genes, Viral The functional hereditary units of VIRUSES. Viral Genes,Gene, Viral,Viral Gene
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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