Lack of immortalizing activity of a human papillomavirus type 16 variant DNA with a mutation in the E2 gene isolated from normal human cervical keratinocytes

The oncogenic potential of a human papillomavirus type 16 (HPV16) variant cloned from normal human cervical keratinocytes has been tested in vitro using primary rodent epithelial cells and human cervical keratinocytes. The HPV16 variant was able to extend the lifespan of, but failed to immortalize,...

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Bibliographic Details
Published in:	Oncogene Vol. 7; no. 3; p. 459
Main Authors:	Storey, A, Greenfield, I, Banks, L, Pim, D, Crook, T, Crawford, L, Stanley, M
Format:	Journal Article
Language:	English
Published:	England 01-03-1992
Subjects:	Amino Acid Sequence Animals Base Sequence Blotting, Northern Cell Differentiation Cell Division Cell Transformation, Viral Cells, Cultured Cervix Uteri - microbiology Cloning, Molecular DNA Mutational Analysis DNA-Binding Proteins - genetics Female Gene Expression Regulation, Viral Humans In Vitro Techniques Keratinocytes - microbiology Molecular Sequence Data Papillomaviridae - genetics Papillomaviridae - pathogenicity Rats Trans-Activators - genetics Transcriptional Activation Viral Proteins - genetics
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Summary:	The oncogenic potential of a human papillomavirus type 16 (HPV16) variant cloned from normal human cervical keratinocytes has been tested in vitro using primary rodent epithelial cells and human cervical keratinocytes. The HPV16 variant was able to extend the lifespan of, but failed to immortalize, human keratinocytes. It could however cooperate with an activated ras oncogene to transform primary rodent cells. Radioimmunoprecipitation assays of the rodent cells showed that they expressed the E7 protein. DNA sequence analysis of the URR/E6/E7 and E5 regions of the HPV16 showed them to be fully functional, but a deletion in the viral E2 open reading frame was detected. This truncated E2 only weakly stimulated transcription of the viral regulatory region. Complementation assays using the HPV16 variant and a full-length E2 enabled the cloned variant to immortalize human cervical keratinocytes with wild-type efficiency. These results suggest that other viral gene products in addition to E6/E7 may play an important role in the in vitro immortalization of cervical keratinocytes in HPV16 and the development of cervical cancer.
ISSN:	0950-9232